Table 1.

Characteristics of the different adoptive T-cell transfer (ACT) therapies.

	First-generation ACT: TIL therapy	Second-generation ACT: engineered T-cell therapy	Third-generation ACT: gene-edited T-cell therapy and personalized therapy
Pre-existing immunity	Yes	No	Depends on the antigens targeted
Antigen targeted	Unknown	Tumor associated antigens: germline antigens, differentiation antigens, antigens overexpressed in tumors, common cancer-specific mutations, etc.	Any tumor-associated antigens or neoantigens
Limited to available HLAs	No	Yes (except for CAR T-cell therapies)	No
Cancer-specific receptors	Endogenous TCRs	Exogenous TCRs or CARs	Exogenous TCRs or CARs replacing T-cell endogenous TCRs
Therapeutic T-cell source	Expanded autologous TILs	Modified autologous peripheral T cells	Modified autologous or heterologous peripheral T cells or heterologous stem cells
Gene-modification method	None (although TILs can be modified with retroviral or lentiviral vectors to express cytokines, etc.)	Retroviral or lentiviral vectors, transposons	CRISPR/Cas9 with linear DNA or adeno-associated viral vectors

CAR, chimeric antigen receptor; CRISPR, clustered regularly interspaced short palindromic repeats; Cas9, CRISPR-associated system; HLA, human leukocyte antigen; TCR, T-cell receptor; TIL, tumor infiltrating lymphocyte.