About this Research Topic
The development, clinical translation and recent efficacy of novel gene therapies targeting refractory malignancies has led to research that extends this technology to a variety of infectious and rheumatological diseases. Unlike conventional drugs or antibodies, T cells have the potential to target and exert effector function in response to disease in a dynamic manner, acting as a “living drug”. The most efficacious form of gene-modified T cells to date is the chimeric antigen receptor (CAR)-modified T cell, which redirects the specificity of T cells to an antigen expressed by tumor cells. Clinical experience with autologous CAR-T cells, primarily in hematologic malignancies, has underscored the feasibility and safety of the approach, while also demonstrating dramatic and sustained antitumor effects through mechanisms orthogonal to those of traditional anticancer therapies. However, several challenging obstacles must be surmounted in order to improve the broader efficacy of this approach.
In this issue, we will address several ongoing challenges related to the generation and optimization of gene-modified T cells, extending from pre-clinical manufacturing to successful clinical translation. Particular attention will be paid to 1) strategies to enhance expansion, persistence and reducing antigen escape in hematological malignancies, 2) effective targeting of solid tumors including combating the immunosuppressive tumor microenvironment and enhancing infiltration and survival in the tumor mass, and 3) pre-clinical validation with clinical translation in mind. We will also explore strategies to successfully navigate the unique safety and regulatory complexities involved with clinical translation of these gene-modified products. This could include analysis of various viral platforms (including good manufacturing production and release criteria) and product modifications aimed at enhancing safety, and clinical trial design.
In this issue, we are looking to receive Original Research, Review, Mini Review, Systematic Review, Methods, Data Report, Perspective and Opinion articles related to the following sub-topics:
• Manufacturing enhancements
• Innovative gene-editing strategies and cellular platforms
• Strategies to enhance in-vivo efficacy and persistence including combinatorial approaches
• Product modifications aimed at improving safety profiles
• Pre-clinical models of gene-modified therapies including toxicity
• New and improved clinical trial design
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.