Table 2.
Immune checkpoints |
Adoptive cellular |
||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Therapeutic approach | CDX 110 | TGF-βAnti-sense | HSP-96 | EGFR Ab | Anti-CTLA-4 | Anti-PD-1PD-L1 | Anti-IL-2Rα | CSF-1R inhibitor | DCs | NK/LAK | CMV T cell | IL13Rα2CAR | IL-12 | ||
Antigen/ Target | Expression frequency | 0–33% (1)34–66% (2)66–100 (3) | 123-25 | 3126 | 3105,127 | 226,128,129 | 110 | 1130 | 315-17,131 | 315-17,131 | 3132,133 | ||||
Benefit in other malignancy | 1 | 1134-136 | 014,137 | 147,138 | 148,139-144 | 159,60 | 1145-147 | 1148-150 | 194 | ||||||
Homogeneous expression | 1 | 1105,127 | 126,128,129 | 157,151 | 116,17,131 | 1132,133 | |||||||||
Persistence at recurrence | 2 | 2152,153 | 2126 | 226,128,129 | 19 | 265 | 265 | ||||||||
Mechanism of resistance | 1 | 1152,153 | 126,128,129 | ||||||||||||
Specificity of expression in the tumor | 1 | 123-25 | 123-25 | 1132,133 | |||||||||||
Immune activation and effector response | Immune activation | 1 | 14,5 | 1127 | 1154 | 1155-157 | 122,31,34,35,37,38,40 | 165 | 1158 | 189-91 | |||||
Trafficking to the tumor | 1 | 1159 | 1105 | 1155-157 | 18 | 158,160,161 | 122,34,35,37,40 | 165 | 1158 | 189,91 | |||||
Maintenance of effector response within tumor | 1 | 1105 | 18,157 | 18,162 | 122,34,35,37,40 | 1158 | 189 | ||||||||
Agent:Preclinical | Anti-stem cell activity | 2 | 2163,164 | 2165 | 2166-168 | 2169 | 292 | ||||||||
Efficacy in preclinical models | Other (1)Clone (1)Xenograft/*GEMM (2) | 1170,17124 | 143-452164 | 11652154 | 28,155,172,173 | 28,162 | 1532174 | 158,160158,160258,160 | 122122,34,35,37,40222 | 1175-1772178,179 | 161,65 | 11692158 | 189,90289,90,180 | ||
Acceptable toxicity profile | 2 | 24,159,181 | 2182 | 2105 | 2154,183 | 247,184-190 | 248,49,139-144 | 254,174 | 258,60,160 | 222,40,98,191-195 | 262,63 | 265 | 270 | 290,93,196 | |
Hits target in vivo | 2 | 24,197 | 28,172,173 | 28,162 | 2174 | 258,160 | 222,37 | 2178,179 | 2158,169 | 290 | |||||
Agent: Clinical | Clinical activity in GBM | 3 | 327,29 | 346 | 3104,105 | 354 | 322,30-35,98 | 362-64 | 360,64 | 370 | |||||
Extreme responders | 2 | 229 | 245 | 2104 | 2198 | 248 | 222,30,31 | 260,64 | |||||||
Combinatorial data | 2 | 228,29 | 2104 | 0183,199 | 251 | 254 | 222,30-33 | 261 | |||||||
Acceptable phase I safety data | 2 | 2159,181 | 246,200 | 2105 | 2183,199 | 247,138,184-190 | 248,49,139-144 | 254 | 260 | 222,30-33 | 262-64 | 265 | 270 | 294 | |
Score | 23 | 20 | 18 | 16 | 16 | 15 | 14 | 14 | 30 | 12 | 19 | 23 | 15 |
Abbreviation: *GEMM, genetically-engineered murine model (of glioma).