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Clinical trials of CAR-T cells in China


Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications. Multi-target CAR-engineered T cells are also entering clinical trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new frontiers in CAR-T cell development. In this study, we analyzed the characteristics of CAR constructs and registered clinical trials of CAR-T cells in China and provided a quick glimpse of the landscape of CAR-T studies in China.


Novel immunotherapeutic agents targeting CTLA-4, programmed cell death-1 protein receptor (PD-1), and the ligand PD-L1 are revolutionizing cancer therapy [1,2,3,4,5,6,7]. Cancer immunotherapy by re-igniting T cells through blocking PD-1 and PD-L1 is highly potent in a variety of malignancies [8,9,10,11,12]. Allogeneic hematopoietic stem cell transplantation has been proven to be a curative immunotherapy for leukemia though with significant toxicities [13,14,15,16,17,18]. Autologous T cells with re-engineered chimeric antigen receptors (CAR-T) have been successfully used for leukemia and lymphoma without graft-vs-host diseases [19,20,21,22,23,24,25]. The first such product, tisagenlecleucel, has recently been approved for clinical therapy of refractory B cell acute lymphoblastic lymphoma (ALL). More and more clinical trials of CAR-T cells are being done throughout the world [26,27,28,29,30,31,32,33,34,35,36,37,38].

In recent years, more and more clinical trials from China are being done and registered in CAR-T cells have become a major source of cellular immunotherapy in China. This study summarized the CAR-T clinical trials being conducted in China and provided a quick glimpse of the landscape of CAR-T studies in China.


We searched using keywords “CAR T,” “CAR-T,” “chimeric antigen receptor,” “adoptive therapy,” “third generation chimeric,” and “fourth generation chimeric”; country: China. All relevant trials registered at the prior to July 18, 2017, were included in the analysis. One trial was excluded (NCT03121625) because the target antigen was not disclosed. A search of the PubMed database was also done to include those trials and cases that have been published.


Distribution of CAR-T trials in China

Currently, there are 121 trials reported and/or registered at from China (Table 1). The trials are mainly carried out in leading hospitals from Beijing, Shanghai, Guangzhou, and Chongqing. CAR-T trials are started in hospitals throughout China. In this study, to avoid duplication of trials that can lead to miscalculation, those trials in Chinese registries were not included. It is possible that the number of institutions carrying out CAR-T trials will increase at a slower pace once regulatory policies are in place. We believe these CAR-T cells should be regulated as drugs [39].

Table 1 Distribution of clinical trials with CAR-T cells in China

Chimeric antigen receptors, vectors, and co-stimulatory molecules used in the CAR constructs

T cell receptors (TCRs) are engineered by incorporating a specific antigen-targeting element and CD3 element to form a completely novel TCR structure, the chimeric antigen receptor (CAR) [35, 40]. In addition, several co-stimulating sequences have been used to facilitate the expansion of the CAR-T cells [41]. CAR-engineered T lymphocytes have been in active clinical development to treat patients with advanced leukemia, lymphoma, and solid tumors [42,43,44,45].

One of the major hurdles in CAR-targeted cellular therapy has been the limited cell dose due to the lack of adequate in vivo cell expansion. Co-stimulatory signals can enhance immune responses of effector T cells [46]. Inducible co-stimulatory signal (ICOS), 4-1BB (CD137), CD28, OX40 (CD134), CD27, and DAP10, along with CD3ζ, have been investigated [31, 47,48,49,50]. Among these, 4-1BB (CD137), CD28, and CD3ζ are the most commonly used COS elements in the CARs (Tables 2, 3, and 4) [51, 52].

Table 2 Clinical trials of CD19-directed CAR-T cells in China
Table 3 Clinical trials of CAR-T cells targeting non-CD19 antigens in China
Table 4 Clinical trials of CAR-T cells for solid tumors in China

Most CARs in the CAR-T trials in China are second-generation CAR constructs, which have one co-stimulatory signal [41]. A trial of CAR-T cells containing a third-generation CAR construct with both CD28 and CD137 co-stimulatory signals is still recruiting patients with relapsed/refractory ALL (NCT02186860). Fourth-generation CARs have incorporated additional elements in the CAR constructs, such as an inducible caspase-9 gene element that can lead to self-destruction by apoptosis of the CAR-T cells [53]. A total of 10 trials of CAR-T cells contain a fourth-generation CAR (Table 5). Among these, five trials are evaluating CARs with an inducible caspase-9 suicide switch.

Table 5 Clinical trials of CAR-T cells with fourth-generation CARs in China

The recombinant CAR cassette is typically packaged into a pseudo-lentivirus vector which can efficiently incorporate into the genome of T cells. To date, the lentiviral vector is the most commonly used vector in CAR-T cells. The other vector commonly used is the retroviral vector (Tables 2, 3, and 4).

Antigen targets

By altering a specific antigen-targeting element, the specificity of the CAR-T cells can be easily re-directed to a specific type of malignancy. This makes the CAR-T cell therapy highly versatile. A number of antigens have been targeted in this way. More and more antigens are being engineered into CAR-T cells, leading to a large repertoire of CAR-T cells that are being explored for the therapy of both solid and hematological malignancies (Tables 3 and 4).

CD19 is the most commonly targeted antigen to date (Table 2). Out of the 121 trials, 57 trials have CD19 as a target. Currently, there are 19 clinical trials in China targeting non-CD19 antigens, including CD20, CD22, CD30, CD33, CD38, CD123, CD138, BCMA, and Lewis Y antigen for hematological malignancies (Table 3). Dual- and multi-specificity CAR-T cells have also been in clinical trials in China.

Current trials on hematological malignancies

The most common type of diseases in CAR-T trials are B cell malignancies, including leukemia, lymphoma, and myeloma.

The CD19-targeted autologous CAR-T product, tisagenlecleucel, was recently approved by FDA for therapy of refractory/relapsed (r/r) B cell ALL. In 30 patients including children and adults who received this product, 90% of them achieved complete remission (CR) [54]. Severe cytokine-release syndrome (CRS) was reported in 27% of the patients. This product has been in clinical trials for CD19+ B cell malignancies, including CLL, ALL, and lymphoma [21,22,23,24, 54, 55]. In a Chinese study (NCT 02813837), 30 patients (5 children and 25 adults) with r/r ALL were treated with autologous CD-19 CAR-T cells [56]. In this 2017 report of preliminary results of a seven-center clinical trial, CR was 86% and severe CRS was seen in 26% of the patients [56]. Successful outcome has been reported with other CAR-T cells against CD19 antigen in r/r ALL [29, 32, 57,58,59].

The CD19-specific CAR-T cells, axicabtagene ciloleucel (axi-cel, KTE-C19), have been reported to be safe for treatment of aggressive lymphomas including r/r diffuse large cell lymphoma (DLBCL) [25]. In the phase II part of the ZUMA-1 trial, overall response rate (ORR) was 76% (47% CR and 29% PR) at the time of report in the cohort 1 of 51 patients [60]. This product is currently under evaluation by FDA.

CD33 and CD123 are targets on myeloid leukemias. Currently, there are three trials on CAR-T cells targeting CD33 and two trials targeting CD123 antigen in China (Table 3). In the USA, three CAR-T trials targeting CD123 were either terminated (NCT02623582) or suspended (UCART123, NCT02159495, and NCT03190278) at this time.

B cell maturation antigen (BCMA) is an antigen target on myeloma cells. Currently, three trials on BCMA-targeted CAR-T cells are being done in r/r myeloma in China (Table 3). In one of the trials of CAR-T cells targeting BCMA in China, 19 patients with r/r multiple myeloma were evaluable and 7 of the patients were followed for more than 6 months at the time of the report [61]. CRS was observed in 14 (74%) patients. The ORRs were close to 100% in the evaluable r/r myeloma patients. The outcome from the preliminary report was highly encouraging. Complete response was also reported in a case of r/r myeloma patient who received autologous CTL019 cells, even though 99.95% of the myeloma cells were negative for CD19 [38, 62]. It appears therefore that multiple myeloma is highly sensitive to immunotherapy.

There are also a few registered clinical trials that are testing two or more CARs either simultaneously or sequentially. In the trial NCT02846584, patients receive intravenously infused autologous anti-CD19 or anti-CD20 CAR-T cells to treat B cell malignancies. Another trial, NCT02737085, is to explore the sequential therapeutic effect of anti-CD19 and anti-CD20 CAR-T cells in the treatment of DLBCL.

The trial NCT02903810 was planned with a treatment scheme of infusion of equal numbers of anti-CD19 and anti-CD22 CAR-T cells in the treatment of refractory hematologic malignancies. Two trials (NCT03097770 and NCT03098355) target two antigens simultaneously with one CAR construct (Table 2). These trials are ongoing at this time.

Current trials on solid tumors

Multiple solid tumors are being studied in CAR-T clinical trials. At the time of this report, 20 different antigens are being targeted in solid tumor trials (Table 4). GPC3, mesothelin, epidermal growth factor receptor (EGFR), and EpCAM were the most targeted antigens (Table 4). This is consistent with reports from international trials [63,64,65,66,67,68]. Liver cancer remains the most commonly studied solid tumor in China [69]. In a preliminary report of a trial of CAR-T cells against CD133+ epithelial tumors (NCT02541370), 24 patients were enrolled, including 14 patients with sorafenib-refractory hepatocellular carcinoma (HCC), 7 with pancreatic carcinomas, 2 with colorectal carcinomas, and 1 with cholangiocarcinoma [69]. The number of CAR-T cells was found to be inversely related to the CD133+ epithelial cells in peripheral blood. There was a separate report treating refractory cholangiocarcinoma with sequential infusion of two different types of CAR-T cells targeting EGFR and CD133 [70].

Two trials in China are evaluating GD2 antigen-targeted CAR-T cells in neuroblastoma (Table 4). Another two trials are evaluating CAR-T cells against EGFRvIII+ glioblastoma. There was one case report in the literature on rapidly progressing refractory glioblastoma that showed dramatic CR to IL13Rα2-targeted CAR-T cells after repeated infusion [71]. In a separate report, nine patients with refractory EGFRvIII+ glioblastoma received autologous CART-EGFRvIII cells in a pilot study [66]. Interestingly, there was no CRS observed. CAR-T cell infiltration was shown in the resected tumor specimen. This study suggested that the CAR-T cells are safe and immunologically active with tracking capability to the cancer cells in the brain.

Multiple antigens are being explored as targets in solid tumors for CAR-T cells (Table 4). Preliminary reports have been presented and published throughout the world [64, 65, 67, 72]. Outcomes from larger sample size and longer follow-up are clearly needed from these trials.

CAR-T trials for non-malignant diseases

There is currently one clinical trial of autologous CAR-T19 cells for patients with systemic lupus erythematosus (NCT03030976, Table 2). This trial is designed to infuse 1 × 106 cells/kg. More trials are expected to come for non-malignant diseases.


This study analyzed CAR-T trials in China. Most CAR-T trials are employing autologous T cells. CD19 is the most commonly targeted antigen. Therefore, B cell leukemia and lymphoma are the most common malignancies in CAR-T trials. Solid tumors remain a significant challenge for CAR-T therapy [45, 70, 73, 74]. Challenges include selection of target antigens, management of toxicities, and modulation of tumor microenvironment [75, 76]. Loss of CD19 expression is a known mechanism for relapse from CD19-directed CAR-T therapy [77]. The first CAR-T product, tisagenlecleucel, was recently approved. KTE-C19 for large cell lymphoma is under evaluation by FDA [25, 60]. It is unclear which product among many ongoing clinical CAR-T trials in China has independent patent that may lead to final approval for clinical application in China.

It has been well documented that CAR-T cells can cross the blood-brain barrier [23, 78, 79]. CAR-T cells may become an effective therapy for refractory CNS diseases [66, 71, 78,79,80,81]. In addition to trials of single-target CAR-T cells, simultaneous and sequential CAR-T cells are being studied for clinical applications [70]. Multi-target CAR-engineered T cells are also entering clinical trials (Tables 2, 3, and 4).

The currently approved tisagenlecleucel CAR-T therapy relies on transduction of autologous T cells from patients. It is important therefore to be able to reliably obtain and propagate adequate amount of T cells. This may become a major limitation for wide application of this new therapy. Therefore, newer CARs are being actively investigated [41, 82,83,84]. Universal CAR-Ts have been generated by inactivating HLA class I molecules and used successfully in patients [82, 85, 86]. Allogeneic CAR-T cells are entering clinical trials [42, 87]. T cell receptor-engineered CAR-T cells represent another frontier in CAR-T cell development [88,89,90]. It is foreseeable that CAR-T immunotherapy will become a major modality of cancer therapy (Table 5) [91].



Acute lymphoblastic leukemia


Acute myeloid leukemia


B cell maturation antigen




Diffuse large B cell lymphoma




Hodgkin’s lymphoma




Mantle cell lymphoma


Non-Hodgkin lymphoma


  1. 1.

    Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lee CH, Motzer RJ. Immune checkpoint therapy in renal cell carcinoma. Cancer J. 2016;22(2):92–5.

    Article  PubMed  Google Scholar 

  4. 4.

    Lee CK, Man J, Lord S, Links M, Gebski V, Mok T, Yang JC. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung cancer-a meta-analysis. J Thorac Oncol. 2017;12(2):403–7.

    Article  PubMed  Google Scholar 

  5. 5.

    Lee JY, Lee HT, Shin W, Chae J, Choi J, Kim SH, Lim H, Won Heo T, Park KY, Lee YJ, Ryu SE, Son JY, Lee JU, Heo YS. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nat Commun. 2016;7:13354.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ribas A. Releasing the brakes on cancer immunotherapy. N Engl J Med. 2015;373(16):1490–2.

    Article  PubMed  Google Scholar 

  8. 8.

    Davar D, Socinski MA, Dacic S, Burns TF. Near complete response after single dose of nivolumab in patient with advanced heavily pre-treated KRAS mutant pulmonary adenocarcinoma. Exp Hematol Oncol. 2015;4:34.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Dholaria B, Hammond W, Shreders A, Lou Y. Emerging therapeutic agents for lung cancer. J Hematol Oncol. 2016;9:138.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Falchi L, Sawas A, Deng C, Amengual JE, Colbourn DS, Lichtenstein EA, Khan KA, Schwartz LH, O’Connor OA. High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy. J Hematol Oncol. 2016;9(1):132.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Hsueh EC, Gorantla KC. Novel melanoma therapy. Exp Hematol Oncol. 2016;5(1):23.

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot J-M, Nghiem P. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374–85.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Baron F, Labopin M, Ruggeri A, Mohty M, Sanz G, Milpied N, Bacigalupo A, Rambaldi A, Bonifazi F, Bosi A, Sierra J, Yakoub-Agha I, Santasusana JM, Gluckman E, Nagler A. Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood—a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation. J Hematol Oncol. 2015;8:107.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010;16:838–47.

    Article  PubMed  Google Scholar 

  15. 15.

    Baron F, Zachee P, Maertens J, Kerre T, Ory A, Seidel L, Graux C, Lewalle P, Van Gelder M, Theunissen K, Willems E, Emonds M-P, De Becker A, Beguin Y. Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2Gy TBI or ATG plus 8Gy TLI: a phase II randomized study from the Belgian Hematological Society. J Hematol Oncol. 2015;8:4.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091–101.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, Hartzman R, Rizzo JD, Horowitz M, Confer D, Maiers M. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. Registry. N Engl J Med. 2014;371(4):339–48.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Koreth J, Matsuoka K, Kim HT, SM MD, Bindra B, EPI A, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011;365(22):2055–66.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Barrett DM, Liu X, Jiang S, June CH, Grupp SA, Zhao Y. Regimen-specific effects of RNA-modified chimeric antigen receptor T cells in mice with advanced leukemia. Hum Gene Ther. 2013;24(8):717–27.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–18.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.

    Article  PubMed  Google Scholar 

  23. 23.

    Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–33.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Porter DL, Kalos M, Zheng Z, Levine B, June C. Chimeric antigen receptor therapy for B-cell malignancies. J Cancer. 2011;2:331–2.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285–95.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Turtle CJ, Riddell SR, Maloney DG. CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy for B-cell malignancies. Clin Pharmacol Ther. 2016;100(3):252–8.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Turtle CJ, Maloney DG. Clinical trials of CD19-targeted CAR-modified T cell therapy; a complex and varied landscape. Expert Rev Hematol. 2016;9(8):719–21.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Ruella M, Kenderian SS, Shestova O, Fraietta JA, Qayyum S, Zhang Q, Maus MV, Liu X, Nunez-Cruz S, Klichinsky M, Kawalekar OU, Milone M, Lacey SF, Mato A, Schuster SJ, Kalos M, June CH, Gill S, Wasik MA. The addition of the BTK inhibitor ibrutinib to anti-CD19 chimeric antigen receptor T cells (CART19) improves responses against mantle cell lymphoma. Clin Cancer Res. 2016;22(11):2684–96.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Park JH, Brentjens RJ. Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells. Discov Med. 2010;9(47):277–88.

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Wei G, Ding L, Wang J, Hu Y, Huang H. Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017;6(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Perez-Ruiz E, Etxeberria I, Rodriguez-Ruiz ME, Melero I. Anti-CD137 and PD-1/PD-L1 antibodies en route toward clinical synergy. Clin Cancer Res. 2017;23(18):5326-28. doi:10.1158/1078-0432.CCR-17-1799. Epub 2017 Aug 8.

  32. 32.

    Park JH, Brentjens RJ. Are all chimeric antigen receptors created equal? J Clin Oncol. 2015;33(6):651–3.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Brentjens RJ. Are chimeric antigen receptor T cells ready for prime time? Clin Adv Hematol Oncol. 2016;14(1):17–9.

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, Li X, Zhang YJ, Zhang WY, Chen MX, Zhang Y, Feng KC, Liu Y, Li SX, Yang QM, Han WD. Autologous T cells expressing CD30 Chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. 2017;23(5):1156–66.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–98.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Sadelain M, Brentjens R, Riviere I, Park J. CD19 CAR therapy for acute lymphoblastic leukemia. Am Soc Clin Oncol Educ Book. 2015:e360–3. doi:10.14694/EdBook_AM.2015.35.e360.

  37. 37.

    Davila ML, Brentjens RJ. CD19-targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2016;14(10):802–8.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Garfall AL, Maus MV, Hwang WT, Lacey SF, Mahnke YD, Melenhorst JJ, Zheng Z, Vogl DT, Cohen AD, Weiss BM, Dengel K, Kerr ND, Bagg A, Levine BL, June CH, Stadtmauer EA. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N Engl J Med. 2015;373(11):1040–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Li Z, Liu D. Cell therapy must be regulated as medicine. Exp Hematol Oncol. 2016;5(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol. 2016;13(1):25–40.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017;5(1):22.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Cai B, Guo M, Wang Y, Zhang Y, Yang J, Guo Y, Dai H, Yu C, Sun Q, Qiao J, Hu K, Zuo H, Dong Z, Zhang Z, Feng M, Li B, Sun Y, Liu T, Liu Z, Wang Y, Huang Y, Yao B, Han W, Ai H. Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia. J Hematol Oncol. 2016;9(1):131.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Fan D, Li Z, Zhang X, Yang Y, Yuan X, Zhang X, Yang M, Zhang Y, Xiong D. AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells. J Hematol Oncol. 2015;8(1):18.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Nakazawa Y, Matsuda K, Kurata T, Sueki A, Tanaka M, Sakashita K, Imai C, Wilson MH, Koike K. Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia. J Hematol Oncol. 2016;9(1):27.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Song D-G, Ye Q, Poussin M, Chacon JA, Figini M, Powell DJ. Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level. J Hematol Oncol. 2016;9(1):56.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Sanmamed MF, Pastor F, Rodriguez A, Perez-Gracia JL, Rodriguez-Ruiz ME, Jure-Kunkel M, Melero I. Agonists of co-stimulation in cancer immunotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol. 2015;42(4):640–55.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, Campana D, Riley JL, Grupp SA, June CH. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):1453–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Song DG, Ye Q, Poussin M, Harms GM, Figini M, Jr Powell DJ. CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood. 2012;119(3):696–706.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Srivastava RM, Trivedi S, Concha-Benavente F, Gibson SP, Reeder C, Ferrone S, Ferris RL. CD137 stimulation enhances cetuximab-induced natural killer: dendritic cell priming of antitumor T-cell immunity in patients with head and neck cancer. Clin Cancer Res. 2017;23(3):707–16.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Tolcher AW, Sznol M, Hu-Lieskovan S, Papadopoulos KP, Patnaik A, Rasco DW, Di Gravio D, Huang B, Gambhire D, Chen Y, Thall AD, Pathan N, Schmidt EV, Chow LQM. Phase Ib study of Utomilumab (PF-05082566), a 4-1BB/CD137 agonist, in combination with pembrolizumab (MK-3475) in patients with advanced solid tumors. Clin Cancer Res. 2017;23(18):5349-57. doi: 10.1158/1078-0432.CCR-17-1243. Epub 2017 Jun 20.

  51. 51.

    Metzger TC, Long H, Potluri S, Pertel T, Bailey-Bucktrout SL, Lin JC, Fu T, Sharma P, Allison JP, Feldman RM. ICOS promotes the function of CD4+ effector T cells during anti-OX40-mediated tumor rejection. Cancer Res. 2016;76(13):3684–9.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Aspeslagh S, Postel-Vinay S, Rusakiewicz S, Soria JC, Zitvogel L, Marabelle A. Rationale for anti-OX40 cancer immunotherapy. Eur J Cancer. 2016;52:50–66.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Budde LE, Berger C, Lin Y, Wang J, Lin X, Frayo SE, Brouns SA, Spencer DM, Till BG, Jensen MC, Riddell SR, Press OW. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PLoS One. 2013;8(12):e82742.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Schuster SJ, Svoboda J, Nasta SD, Chong EA, Winchell N, Landsburg DJ, Porter DL, Mato AR, Strauser HT, Schrank-Hacker AM, Wasik MA, Lacey SF, Melenhorst JJ, Chew A, Hasskarl J, Marcucci KT, Levine BL, June CH. Treatment with chimeric antigen receptor modified T cells directed against CD19 (CTL019) results in durable remissions in patients with relapsed or refractory diffuse large B cell lymphomas of germinal center and non-germinal center origin, “double hit” diffuse large B cell lymphomas, and transformed follicular to diffuse large B cell lymphomas. Blood. 2016;128(22):3026.

    Google Scholar 

  56. 56.

    Xiao L, Huang H, Huang X, Ke X, Hu Y, Li J, Zhang Q, Hu Y, Jiang Q, Hu J, Jing H, Zhang X, Wu Z. Efficacy of anti-CD19 chimeric antigen receptor modified T(CAR-T) cell therapy in Chinese patients with relapsed/refractory acute lymphocytic leukemia in a multicenter trial. J Clin Oncol. 2017;35(15_suppl):7028.

    Google Scholar 

  57. 57.

    Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, Bartido S, Stefanski J, Taylor C, Olszewska M, Borquez-Ojeda O, Qu J, Wasielewska T, He Q, Bernal Y, Rijo IV, Hedvat C, Kobos R, Curran K, Steinherz P, Jurcic J, Rosenblat T, Maslak P, Frattini M, Sadelain M. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra138.

    Article  Google Scholar 

  58. 58.

    Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016;127(26):3312–20.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Park JH, Riviere I, Wang X, Senechal B, Wang Y, Mead E, Santomasso B, Halton E, Diamonte C, Bernal Y, Li D, Sadelain M, Brentjens RJ. Durable long-term survival of adult patients with relapsed B-ALL after CD19 CAR (19-28z) T-cell therapy. J Clin Oncol. 2017;35(15_suppl):7008.

    Google Scholar 

  60. 60.

    Neelapu SS, Locke FL, Bartlett NL, Lekakis L, Miklos D, Jacobson CA, Braunschweig I, Oluwole O, Siddiqi T, Lin Y, Timmerman J, Stiff PJ, Friedberg J, Flinn I, Goy A, Smith M, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Reagan P, Bot A, et al. Kte-C19 (anti-CD19 CAR T cells) induces complete remissions in patients with refractory diffuse large B-cell lymphoma (DLBCL): results from the pivotal phase 2 Zuma-1. Blood. 2016;128(22):LBA-6.

    Google Scholar 

  61. 61.

    Fan F, Zhao W, Liu J, He A, Chen Y, Cao X, Yang N, Wang B, Zhang P, Zhang Y, Wang F, Lei B, Gu L, Wang X, Zhuang Q, Zhang W. Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. J Clin Oncol. 2017;35(18_suppl):LBA3001.

    Article  Google Scholar 

  62. 62.

    Garfall AL, Stadtmauer EA, June CH. Chimeric antigen receptor T cells in myeloma. N Engl J Med. 2016;374(2):194.

    Article  PubMed  Google Scholar 

  63. 63.

    Koneru M, O'Cearbhaill R, Pendharkar S, Spriggs DR, Brentjens RJ. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. J Transl Med. 2015;13:102.

    Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, Gerken C, Liu E, Dakhova O, Ashoori A, Corder A, Gray T, Wu M-F, Liu H, Hicks J, Rainusso N, Dotti G, Mei Z, Grilley B, Gee A, Rooney CM, Brenner MK, Heslop HE, Wels WS, Wang LL, Anderson P, Gottschalk S. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688–96.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Hassan R, Thomas A, Alewine C, Le DT, Jaffee EM, Pastan I. Mesothelin immunotherapy for cancer: ready for prime time? J Clin Oncol. 2016;34(34):4171–9.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    O'Rourke DM, Nasrallah M, Morrissette JJ, Melenhorst JJ, Lacey SF, Mansfield K, Martinez-Lage M, Desai AS, Brem S, Maloney E, Mohan S, Wang S, Verma G, Navenot J-M, Shen A, Zheng Z, Levine B, Okada H, June CH, Maus MV. Pilot study of T cells redirected to EGFRvIII with a chimeric antigen receptor in patients with EGFRvIII+ glioblastoma. J Clin Oncol. 2016;34(15_suppl):2067.

    Google Scholar 

  67. 67.

    Yeku OO, Purdon T, Spriggs DR, Brentjens RJ. Chimeric antigen receptor (CAR) T cells genetically engineered to deliver IL-12 to the tumor microenvironment in ovarian cancer. J Clin Oncol. 2017;35(15_suppl):3050.

    Google Scholar 

  68. 68.

    Hegde M, Wakefield A, Brawley VS, Grada Z, Byrd TT, Chow KK, Krebs SS, Heslop HE, Gottschalk SM, Yvon E, Ahmed N. Genetic modification of T cells with a novel bispecific chimeric antigen receptor to enhance the control of high-grade glioma (HGG). J Clin Oncol. 2014;32(15_suppl):10027.

    Google Scholar 

  69. 69.

    Wang Y, Chen M, Wu Z, Tong C, Huang J, Lv H, Dai H, Feng K, Guo Y, Liu Y, Yang Q, Han W. CD133-redirected chimeric antigen receptor engineered autologous T-cell treatment in patients with advanced and metastatic malignancies. J Clin Oncol. 2017;35(15_suppl):3042.

    Article  Google Scholar 

  70. 70.

    K-c F, Guo Y-l, Liu Y, Dai HR, Wang Y, Lv HY, Huang JH, Yang QM, Han WD. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017;10(1):4.

    Article  Google Scholar 

  71. 71.

    Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, Ostberg JR, Blanchard MS, Kilpatrick J, Simpson J, Kurien A, Priceman SJ, Wang X, Harshbarger TL, D’Apuzzo M, Ressler JA, Jensen MC, Barish ME, Chen M, Portnow J, Forman SJ, Badie B. Regression of Glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375(26):2561–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    You F, Jiang L, Zhang B, Lu Q, Zhou Q, Liao X, Wu H, Du K, Zhu Y, Meng H, Gong Z, Zong Y, Huang L, Lu M, Tang J, Li Y, Zhai X, Wang X, Ye S, Chen D, Yuan L, Qi L, Yang L. Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified anti-MUC1 chimeric antigen receptor transduced T cells. Sci China Life Sci. 2016;59(4):386–97.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Feng K, Guo Y, Dai H, Wang Y, Li X, Jia H, Han W. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci. 2016;59(5):468–79.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Jin L, Ge H, Long Y, Yang C, Chang YE, Mu L, Sayour EJ, De Leon G, Wang QJ, Yang JC, Kubilis PS, Bao H, Xia S, Lu D, Kong Y, Hu L, Shang Y, Jiang C, Nie J, Li S, Gu Y, Sun J, Mitchell DA, Lin Z, Huang J. CD70, a novel target of CAR-T-cell therapy for gliomas. Neuro-Oncology. 2017;19 doi:10.1093/neuonc/nox116.

  75. 75.

    Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric antigen receptor therapy for cancer. Annu Rev Med. 2014;65:333–47.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016;3:16011.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Gardner R, Wu D, Cherian S, Fang M, Hanafi LA, Finney O, Smithers H, Jensen MC, Riddell SR, Maloney DG, Turtle CJ. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood. 2016;127(20):2406–10.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Hu Y, Sun J, Wu Z, Yu J, Cui Q, Pu C, Liang B, Luo Y, Shi J, Jin A, Xiao L, Huang H. Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy. J Hematol Oncol. 2016;9(1):70.

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Abramson JS, McGree B, Noyes S, Plummer S, Wong C, Chen Y-B, Palmer E, Albertson T, Ferry JA, Arrillaga-Romany IC. Anti-CD19 CAR T cells in CNS diffuse large-B-cell lymphoma. N Engl J Med. 2017;377(8):783–4.

    Article  PubMed  Google Scholar 

  80. 80.

    Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E, Hawkins R, Chaney C, Cherian S, Chen X, Soma L, Wood B, Li D, Heimfeld S, Riddell SR, Maloney DG. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, Robinson E, Steevens NN, Chaney C, Soma L, Chen X, Yeung C, Wood B, Li D, Cao J, Heimfeld S, Jensen MC, Riddell SR, Maloney DG. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126(6):2123–38.

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Ren J, Liu X, Fang C, Jiang S, June CH, Zhao Y. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clin Cancer Res. 2017;23(9):2255–66.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Kebriaei P, Singh H, Huls MH, Figliola MJ, Bassett R, Olivares S, Jena B, Dawson MJ, Kumaresan PR, Su S, Maiti S, Dai J, Moriarity B, Forget MA, Senyukov V, Orozco A, Liu T, McCarty J, Jackson RN, Moyes JS, Rondon G, Qazilbash M, Ciurea S, Alousi A, Nieto Y, Rezvani K, Marin D, Popat U, Hosing C, Shpall EJ, et al. Phase I trials using sleeping beauty to generate CD19-specific CAR T cells. J Clin Invest. 2016;126(9):3363–76.

    Article  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Kunert A, Straetemans T, Govers C, Lamers C, Mathijssen R, Sleijfer S, Debets R. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness, and sensitization of tumor milieu. Front Immunol. 2013;4:363.

    Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, Butler K, Rivat C, Wright G, Somana K, Ghorashian S, Pinner D, Ahsan G, Gilmour K, Lucchini G, Inglott S, Mifsud W, Chiesa R, Peggs KS, Chan L, Farzeneh F, Thrasher AJ, Vora A, Pule M, Veys P. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017;9(374): 10.1126/scitranslmed.aaj2013.

  86. 86.

    Barrett DM, Grupp SA, June CH. Chimeric antigen receptor- and TCR-modified T cells enter main street and wall street. J Immunol. 2015;195(3):755–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Brudno JN, RPT S, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, Feldman SA, Iwamoto AT, Kurlander R, Maric I, Goy A, Hansen BG, Wilder JS, Blacklock-Schuver B, Hakim FT, Rosenberg SA, Gress RE, Kochenderfer JN. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34(10):1112.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Debets R, Donnadieu E, Chouaib S, Coukos G. TCR-engineered T cells to treat tumors: seeing but not touching? Semin Immunol. 2016;28(1):10–21.

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Ping Y, Liu C, Zhang Y. T-cell receptor-engineered T cells for cancer treatment: current status and future directions. Protein Cell. 2017;8

  90. 90.

    Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, Badros AZ, Garfall A, Weiss B, Finklestein J, Kulikovskaya I, Sinha SK, Kronsberg S, Gupta M, Bond S, Melchiori L, Brewer JE, Bennett AD, Gerry AB, Pumphrey NJ, Williams D, Tayton-Martin HK, Ribeiro L, Holdich T, Yanovich S, Hardy N, Yared J, Kerr N, Philip S, Westphal S, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914–21.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Rosenbaum L. Tragedy, perseverance, and chance—the story of CAR-T therapy. N Engl J Med. 2017;377(0): 10.1056/NEJMp1711886.

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This study was partly supported by Henan Cancer Hospital and The Affiliated Cancer Hospital of Zhengzhou University.


This project was partly supported by the Zhengzhou University training fellowship (BL) and by the National Natural Science Foundation of China (NSFC grant no. 81470287, YPS). BL is a recipient of the 2017 CAHON Young Investigator Award (

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DL designed the study. All authors drafted the manuscript. All authors read and approved final manuscript.

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Correspondence to Yongping Song or Delong Liu.

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Liu, B., Song, Y. & Liu, D. Clinical trials of CAR-T cells in China. J Hematol Oncol 10, 166 (2017).

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  • Chimeric Antigen Receptor (CAR-T)
  • Tisagenlecleucel
  • B-cell Maturation Antigen (BCMA)
  • Axicabtagene Ciloleucel
  • Fourth-generation CAR