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] |