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

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]