Table 2. Opportunities for improving ACT for the treatment of human cancer.

ACT, adoptive cell therapy; APC, antigen-presenting cell; CTLA4, cytotoxic T-lymphocyte-associated 4; IL, interleukin; PD-1, programmed death 1; TCR, T-cell receptor.

Method	Approach	Example refs
Genetic modification of lymphocytes to introduce new recognition specificities	αβTCR, chimeric TCR	4
Genetic modification of lymphocytes to alter function of T cells	Use of co-stimulatory molecules (CD28, 41BB); cytokines (IL2, IL15); homing molecules (CD62L, CCR7); prevention of apoptosis (BCL2)	76
Modify host lymphodepletion	Selective depletion of CD4+ cells or T regulatory cells	23
Block inhibitory signals on reactive lymphocytes	Antibodies to CTLA4 or PD-1	9
Administer vaccines to stimulate transferred cells	Recombinant virus encoding antigen	22
Administer alternative cytokines to support cell growth	IL15, IL21	77
Stimulate APCs	Use of Toll-like receptor agonists	27
Generate less differentiated lymphocytes	Alternate culture conditions and growth promoting cytokines in vitro	26
Overcome antigen escape variants	Use of natural killer cells	78