Table 1.

Characteristics of different T-cell therapies for cancer

TILsTCRsCARsBispecific antibodiesCheckpoint inhibitors
Type of therapyACTACTACTAntibodyAntibody
DrugUnmodified (naturally occurring) T cells isolated form tumors and expanded ex vivoT cells genetically engineered ex vivo from peripheral T cells to express recombinant TCR against a tumor AgT cells genetically engineered ex vivo from peripheral T cells to express a CAR (scFv with TCR signaling molecules) against a tumor surface AgT-cell engaging bispecific antibodies directed against a tumor surface Ag and CD3Antibodies blocking inhibitory molecules on T cells to enhance their function
Requirement for tumor Ag identificationNoYesYesYesNo
Specificity against tumor cellsPolyclonalMonoclonalMonoclonalMonoclonalPolyclonal
Origin of Ag targetedIntracellular and extracellularIntracellular (MHC-I–restricted T cells)SurfaceSurfaceIntracellular and extracellular
MHC-restrictedYesaYesaNoNoNo
Long-lasting protectionYesYesYesNoYes
Off-the-shelfNoNoNoYesYes
Personalized therapy++++b++++++None
Main limitationsFeasibility Mostly restricted to melanomaOn-target/off-tumor toxicityOn-target/off-tumor toxicityCNS toxicity (with CD19/CD3 antibody)Autoimmune manifestations
CRS
Tumor escape (loss of surface Ag)

Abbreviations: Ag, antigen; CRS, cytogen release syndrome.

  • aHLA-negative tumors are not “seen,” but HLA presentation allows recognition of intracellular antigens.

  • bPlus signs indicate degree of personalization.