Translation of Genetically Engineered T cells in Cancer Immunotherapy

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Background

Genetically engineered T cells have made tremendous contributions to cancer immunotherapy. Cancer patients with hematological malignancies treated with chimeric antigen receptor (CAR)-modified T cells have obtained remarkable clinical efficacy, however, for solid tumors, CAR-T cells have not been very effective. The T cell receptor (TCR)-engineered T cells have shown some degree of efficacy in treating solid tumors, nonetheless, current results are far from satisfactory. Several challenges need to be overcome to translate the current genetically engineered T cells into the clinics as an effective therapeutic approach. For example, the genetically engineered T cells need to be persistent in the patient to maintain a long-lasting immunosurveillance against tumors and keep the patient in relapse-free survival. To achieve tumor eradication, the genetically engineered T cells not only need to migrate and penetrate into the solid tumors, but also need to overcome the immunosuppressive effects of the tumor microenvironment (TME), and finally to fulfill the goal of specific recognition and targeted destruction of the tumor cells.
In this Research Topic, we would like to address these challenges starting from targeting tumor-specific neoantigens, to the generation and optimization of genetically modified T cells, so that such engineered T cells can persist in the patient to maintain a long-lasting immunosurveillance, but at the same time can also migrate and penetrate into the solid tumors, and have the ability to resist the immunosuppressive effects of the TME, thus to achieve the ultimate goal of specific recognition and targeted destruction of the tumor cells.
We are looking for robust pre-clinical manufacturing platforms, as well as successful clinical translations. We would also like to explore strategies for navigating the regulatory complexities involved in the clinical translation of these genetically engineered T cells. This could include analysis of various viral platforms (including good manufacturing practice and release criteria) and product modifications aimed at enhancing the safety and efficacy of the clinical trial.
In this issue, we welcome the submission of Original Research, Review, Mini Review, Systematic Review, Methods, Data Report, Perspective, and Opinion articles related but not limited to, the following aspects:
1) Identification and validation of novel tumor-specific neoantigens used for immunotherapy and cancer vaccines;
2) Novel strategies for genetic engineering of T cells, including CAR-T and TCR-T cells;
3) Strategies to enhance expression, specificity, affinity, and (signaling) functions of the engineered molecules;
4) Tactics for enhanced expansion and persistence of the engineered T cells;
5) Strategies for attracting the engineered T cells to migrate and penetrate into solid tumors, and become resistant to TME suppression;
6) Strategies for reducing toxicity and improving safety;
7) Manufacturing platforms for vector production and cellular engineering;
8) Research of pre-clinical investigations and validations as well as clinical translations.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Cancer Immunotherapy, Genetic Engineering, Tumor Targeting, Neoantigen, chimeric antigen receptor (CAR), T-cell receptor (TCR)

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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