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Table 2 Pipeline development: TCR-based therapy programs and their targets

From: T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors

Company/institution

TCR program(s) (investigational)

Target

Indication(s)

Key features

Adaptimmune

ADP-A2M4 SPEAR T-cells

MAGE-A4

Synovial Sarcoma

TCR (ADP-A2M4) targeting metastatic or inoperable (advanced) Synovial Sarcoma or MRCLS who have received prior chemotherapy and whose tumor expresses the MAGE-A4 tumor antigen. Evaluating urothelial (bladder) cancers, melanoma, head and neck cancer, ovarian cancer, NSCLC, esophageal cancer, gastric cancers, synovial sarcoma, and Myxoid Round Cell Liposarcoma (MRCLS). Adapted to mixed solid tumors secondary studies

Adaptimmune

ADP-A2M4CD8 SPEAR T-cell

MAGE-A4

Solid Tumors

TCR (ADP-A2M4CD8) which also expresses the CD8α co-receptor alongside the engineered TCR that targets MAGE-A4. Preclinical data indicate that co-expression of CD8α may broaden the immune response against solid tumors and increase antitumor activity by leveraging CD4 + cells into CD8 + killer or cytotoxic T-cells while retaining their CD4 + helper function

Adaptimmune

ADP-A2M10 T-cell

MAGE-A10

NSCLC, Melanoma, Bladder, Head and Neck

TCR (ADP-A2M10) targeting MAGE-A10 with potential ability to bind target peptides from multiple cancer types

Adaptimmune

ADP-A2AFP SPEAR T-cell

AFP

Hepatocellular Carcinoma

TCR (ADP-A2AFP) in SPEAR T-cell product which targets alpha-fetoprotein (AFP). Currently in Phase I clinical trial for the treatment of patients with hepatocellular carcinoma (liver cancer)

Bluebird Bio

MCC1 TCR

MCPyV

Merkel cell carcinoma

Autologous CD4 + and CD62L-expressing CD8 + T-cells expressing the high affinity T-cell receptor (TCR) A2-MCC1, specific for the human leucocyte antigen (HLA)-A02-restricted Merkel cell polyomavirus (MCPyV; MCV) viral oncoprotein. Final product is a cytotoxic T-lymphocyte (CTL) that targets tumor cells expressing the MCPyV viral oncoprotein. MCPyV viral oncoprotein is highly expressed in Merkel cell carcinoma (MCC) caused by MCPyV

Bluebird Bio/Medigene

MAGE-A4 TCR

MAGE-A4

Solid Tumors/Melanoma

Autologous human T lymphocytes transduced with MAGE-A4 as a co-receptor-independent TCR. After isolation, transduction, expansion, and reintroduction, MAGE-A4-specific TCR gene-transduced T lymphocytes bind to tumor cells expressing MAGE-A4. Effecting mechanism both inhibiting growth and increased cell death for MAGE-A4-expressing tumor cells. MAGE-A4 is overexpressed by a variety of cancer cell types

Kite/Gilead Sciences

KITE-718

MAGE-A3 and/or MAGE-A6

Solid Tumors/Advanced Cancers

Genetically modified T-cells which target tumor cells that express MAGE-A3 and/or MAGE-A6 in patients with solid tumors with relapsed or refractory disease after a systemic standard of care treatment

Kite/Gilead Sciences

KITE-439

HPV16 E6 and HPV16 E7

Solid Tumors/Advanced Cancers

Genetically modified T-cells which target cells that express HPV16 + solid tumors in patients with relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and not amenable to locoregional definitive therapy

Kite/Gilead Sciences

KITE-439

HPV16hat HOV

Solid Tumors/Advanced Cancers

Genetically modified T-cells which target cells that express HPV16 + solid tumors in patients with relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and not amenable to locoregional definitive therapy

Immatics

IMA201-101

MAGE-A4/8

Solid Tumors

ACTengine IMA201 genetically engineered T-cells (TCR-T) targeting MAGE-A4 or MAGE-A8 in patients with various solid tumors, including HNSCC, squamous NSCLC, subtypes of sarcoma and other solid tumor indications

Immatics

IMA202-101

MAGE-A1

Solid Tumors

ACTengine IMA202 genetically engineered T-cells (TCR-T) targeting MAGEA1 in patients with diverse solid tumors, including squamous NSCLC, hepatocellular carcinoma (HCC) and others

Immatics

IMA203-101

PRAME

Solid Tumors

ACTengine IMA203 genetically engineered T-cells (TCR-T) targeting PRAME in patients with a broad range of solid tumor types, including uterine cancer, ovarian cancer, melanoma, subtypes of sarcoma, squamous NSCLC and others

Juno

JTCR016

WT1

Stage III/IV NSCLC

Mesothelioma

Autologous CD8 + T-cells genetically-modified to express a high affinity WT1-specific T-cell receptor targeting tumors in patients with stage III-IV non-small cell lung cancer (NSCLC) or mesothelioma

TCR2 Therapeutics

TC-210

Mesothelin

Ovarian Cancer, NSCLC, MPM, Cholangiocarcinoma

TCR-based adoptive therapy which targets mesothelin-positive solid tumors. Mesothelin is highly expressed in solid tumors and has a correlation with poor prognosis and tumorigenesis

Tmunity

NY-ESO-1 TCR-T

Triple Knockout TCR (NYCE)

NY-ESO-1

Melanoma/Synovial Sarcoma

TCR-based adoptive therapy (NYCE) targeting NY-ESO-1 with designated target-binding capacity in melanoma and synovial sarcoma tumor types

Tmunity

H3.3K27M TCR

H3.3K27M

Diffuse intrinsic pontine glioma

Human T-cells transduced with a TCR that specifically targets the H3.3.K27M epitope and kills HLA-A2 + H3.3.K27M + glioma cells both in vitro and in vivo

Ziopharm

Sleeping Beauty TCR-T Targeting Neoantigens

NY-ESO-1

Personalized TCR-T

(3 programs)

Multiple Solid Tumors

Genetically modified TCR therapies that target neoantigens. Sleeping Beauty’s non-viral (transposon/transposase) gene transfer system is suited for developing genetically modified TCR therapies that target neoantigens because of its very rapid manufacturing capability