Skip to main content

Table 2 Most frequently targeted antigens, and clinical examples of application

From: CAR-T cells and BiTEs in solid tumors: challenges and perspectives

  Expression in normal tissue Expression in solid tumors CAR-T examples BiTEs examples References
HER2 Low expression in normal tissue Overexpression in selected solid tumors Responses seen in biliary tract cancer, rhabdomyosarcoma, mostly partial;
1 toxic death reported
14 patients treated, 1 response [8, 73, 74, 101, 102]
EGFRvIII No expression in normal tissue Specific mutation present in some glioblastoma 18 glioblastoma patients: median PFS of 1.3 months, 1 outlier
1 long responder after intraventricular injection
Acquired resistance after 1 injection through antigen loss
No toxicity
1 response in 8 evaluable patients [17, 81, 103, 104]
Mesothelin Low expression in normal tissue Expression in some solid tumors 18 mesothelioma patients treated in combination with anti-PD1: 2 complete responses and 5 partial responses
No toxicity
50 treated patients, no response [83, 105]
GD2 Very limited expression in normal tissue Constant in neuroblastoma 6 patients treated, some responses in 3 patients. No toxicity Only preclinical [106]
Glypican-3 Low expression in normal tissue Frequent expression in hepatocellular carcinoma, expression in selected tumors 13 HCC patients treated, 2 partial responses
1 grade 5 CRS
Phase 1 ongoing [31, 107]
CEA (CEACAM5) Low expression in normal tissue Expression in multiple solid tumors 10 patients treated: 2 partial metabolic responses
No severe toxicity
2 responders among 11 patients treated in combination with anti-PD-L1 [88, 108]
PSMA Low expression in normal tissue Frequent expression in prostate 2 of 5 patients had a partial response. No toxicity 3 responders among 15 patients treated in a dose-escalation trial [33, 34]
Claudin 18.2 Low expression in normal gastric tissue Expression in some solid tumors 4 partial responses among 10 patients treated. 3 grade 2 on-target gastric toxicities Phase 1 ongoing [37, 39]
EpCAM Low expression in normal tissue Expression in multiple solid tumors Only preclinical Catumoximab: Demonstrated efficacy of intraperitoneal injection to control the symptoms of peritoneal carcinomatosis
Severe gastrointestinal toxicity precluding further development of this drug
[12, 109]
AFP (intracellular) Low expression in normal tissue Expression in hepatocellular carcinoma and some other tumors Partial responses described with 2 different TCR-engineered T cells targeting AFP Not applicable [51, 110]