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.

Taming the T Cell

“…These second-generation CARs display an increase in T-cell proliferation, anti-apoptotic protein and cytokine release [4]. The third generation simply introduced a further costimulatory signal, while the fourth involves additional stimulation of transcription factors to induce the production and secretion of specific cytokines and interleukins in order to promote the potency of T-cell action [5]. The scope of these additional functional transgenic proteins in the fourth generation does not end with the simple amplification of T-cell potency.…”

“…To further promote CAR-T cells as a viable therapeutic option capable of surviving in the TME, researchers have developed dual receptor CAR-T cells that contain the traditional TAA targeting CARs and an additional receptor for cytokine-mediated growth stimulation helping to offset the effects of the immune checkpoint signals in the TME [5].…”

“…Minutes after the administration of 10 11 HER2-targeted CAR cells, the patient experienced extreme pain and entered a comatose state from which they did not recover, dying 5 days later. It is likely that the natural presence of HER2 in pulmonary epithelial cells was a significant factor in the observed accumulation of CAR-T cells in the patient's lungs [5].…”

“…Demonstrating the different binding modalities of (A) classical CAR-T cells, (B) simultaneous and (C) sequential UIRs[5].No. 2 | Vol.…”

Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research

“…Neoantigens are derived from the genetic alteration of somatic cells, and can be targeted by the immune system to control malignancies (3). The last 30 years have witnessed the rapid development of adoptive cell therapy, as two critical parts of immunotherapy, CAR-T therapy, and TCR-T therapy, hold the promising possibility to cure cancer (4). Limited by severe adverse effects, the two kinds of immunotherapies need to be improved, and the screening and application of neoantigens is an effective way to enhance the specificity of CAR-T and TCR-T and minimize their side effects.…”