T Cell Based Immunotherapy for Cancer: Approaches and Strategies

Abstract

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progress has been made in T cell-based immunotherapy over the past decade, using naturally occurring or genetically engineered T cells to target cancer antigens in hematological malignancies and solid tumors. However, limited specificity, longevity, and toxicity have limited success rates. This review provides an overview of T cells as a therapeutic tool for cancer, highlighting the advantages and future strategies for developing effective T cell cancer immunotherapy. The challenges associated with identifying T cells and their corresponding antigens, such as their low frequency, are also discussed. The review further examines the current state of T cell-based immunotherapy and potential future strategies, such as the use of combination therapy and the optimization of T cell properties, to overcome current limitations and improve clinical outcomes.

Keywords: CAR MIAT; CAR NK cells; HLA restriction; T cells; TCR engineering; cancer antigens; chimeric antigen receptor; immunotherapy; neoantigens.

Figure 1

Different strategies of T cell immunotherapies. (A) Isolation of tumor-infiltrating lymphocytes from patient tumor followed by expansion of anti-tumor T cells in vitro and infusion back to the patients. (B) Generation of antigen-presenting cells from monocytes derived from patient PBMC and loaded with potential antigens derived from the mutational and immunopeptidome analysis of patient tumor. The antigen-loaded APC are co-cultured with autologous T cells that are screened for anti-tumor T cells and further expanded. (C) TCR is cloned and used to gene-engineer TCR in fresh autologous or allogeneic T cells for expansion in laboratory conditions and infusion back to the patient. (D) Isolation of T cells from patient or allogeneic donor and gene-editing approaches for engineering of chimeric antigen receptors targeting cancer cells.