Engineered T Cell Therapy for Cancer in the Clinic

Abstract

T cells play a key role in cell-mediated immunity, and strategies to genetically modify T cells, including chimeric antigen receptor (CAR) T cell therapy and T cell receptor (TCR) T cell therapy, have achieved substantial advances in the treatment of malignant tumors. In clinical trials, CAR-T cell and TCR-T cell therapies have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. This article summarizes the current applications of CAR-T cell and TCR-T cell therapies in clinical trials worldwide. It is predicted that genetically engineered T cell immunotherapies will become safe, well-tolerated, and effective therapeutics and bring hope to cancer patients.

Keywords: CAR-T cell; TCR-T cell; clinic; engineered T cells; immunotherapy.

Figure 1

A brief flow chart of engineered-T cell therapy. A sufficient amount of blood is drawn from patients to obtain enough peripheral blood mononeuclear cells (PBMCs) for engineered T cell manufacturing. The T cells are purified from patients PBMCs. After activation and amplification in vitro, T cells are modified by viral vector transfection, such as lentivirus transfection or retrovirus transfection, to express specific CARs/TCRs on the T cell surface. Following amplification and quality control, CAR-T cells/TCR-T cells are infused into the patient body to improve antitumor ability.

Figure 2

Schematic diagram of the CAR-T cell structure. In the first generation of CARs, there was only one intracellular signal component CD3ζ. The second generation of CAR added one costimulatory molecule on the basis of the first generation. Based on the second generation of CARs, the third generation of CAR added another costimulatory molecule. Fourth-generation of CAR T cells can activate the downstream transcription factor to induce cytokine production after the CAR recognizes the target antigens. The fifth-generation of CARs, based on the second generation, uses gene editing to inactivate the TRAC gene, leading to the removal of the TCR alpha and beta chains.

Figure 3

Current clinical targets for CAR-T treatment of hematologic malignancies. The pie chart is based on the statistical result of CAR-T clinical trials for hematologic malignancies registered on ClinicalTrials.gov.

Figure 4

Current clinical targets for CAR-T therapy in solid tumors. The pie chart is based on the statistical result of CAR-T clinical trials for solid tumors registered on ClinicalTrials.gov.

Figure 5

Schematic diagram of the CAR-T cell structure. The TCR complex is a heterodimer consisting of two different peptide chains, TCRα and TCRβ, and is surrounded by four CD3 chains. The MHC class I molecules present intracellular antigenic peptides of cancer cells for recognition bt the T cell receptor.

Figure 6

Current clinical targets for TCR-T therapy in solid tumors (ClinicalTrials.gov). The pie chart is based on the statistical result of TCR-T clinical trials for solid tumors registered on ClinicalTrials.gov.