Adoptive T cell therapy for solid tumors: current landscape and future challenges

Abstract

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors.

Keywords: T cells; TCR-modified cells; TIL therapy; adoptive cell therapy; car-t; immunotherapy; melanoma.

Figure 1

Mechanisms of anti-tumor response; (A) Innate immunity; (B) Adaptive immunity (priming phase); (C) Adaptive immunity (effector phase). TAA, tumor-associated antigen; DAMPs, damage-associated molecular patterns; TCR, T cell receptor; MHC, major histocompatibility complex; IL-12, interleukin-12; IFN, interferons.

Figure 2

Clinical outcomes of the most relevant CAR-T cells phase I/II trials in solid tumors. N, number of participants in each study.