Adoptive T cell therapy: points to consider

•Adoptive cellular therapy is represented by 3 major modalities: tumor-infiltrating lymphocyte therapy, CAR/TCR-engineered cell therapy and endogenous T cell therapy.•CAR T cell therapy directed to CD19 demonstrated remarkable efficacy and long-lasting benefit for patients with B cell malignancies.•The in vivo persistence of transferred T cells and development of multivalent responses are associated with a favorable clinical response.•Combination strategies to enhance ACT will use other modalities such as immune checkpoint blockade, agonist antibodies, vaccines and other immune based approaches. Adoptive Cell Therapy (ACT) has enjoyed a revival in recent years with the approval of CAR T cells for the treatment of patients with B cell malignancies. Advancing the use of adoptively transferred T cells for the treatment of patients with solid tumor and other hematologic malignancies however, will require addressing numerous effector cell intrinsic as well as tumor micro environmental hurdles and exploiting a broader ACT platform that includes not only engineered CAR-T cells, but also other forms of ACT including Endogenous T Cell (ETC) and Tumor-infiltrating Lymphocyte (TIL) therapy. In this review, we open this discussion with some ‘points to consider’ as a starting point for envisioning more effective strategies that are now feasible because of recent discoveries In immune resistance and the development of enabling technologies to harness the power of tumor - reactive T cells for adoptive cell therapy.