About this Research Topic
This Research Topic is the second volume of the “Optimized Gene-Engineering and Combination Therapies to Boost γδT Cell Immunotherapeutic Performance” Community Series. Please see Volume I here.
γδT cell-based immunotherapies for cancer offer a promising and allo-compatible alternative to classical CAR-αβT approaches, hampered by complex autologous manufacturing logistics and poor efficacy against solid tumor indications. Despite much pre-clinical promise, however, early data from unmodified autologous and allogeneic γδT cell clinical trials of various γδT cell subsets has been largely underwhelming. Data suggests that - much like other adoptive cell therapy substrates - γδT cells too are sensitive to suppression by the tumour microenvironment, functional exhaustion and suffer from a lack of persistence. In the pursuit of transformational γδT cell immunotherapeutic efficacy, it is increasingly apparent that gene-engineering and combination therapies will be indispensable.
As appreciation of the need for gene-engineering and therapeutic combinations grows, the volume of literature evaluating γδT cell engineering strategies and combinations remains low. Direct comparisons between unmodified γδT cells of various subsets and engineered counterparts are rare. Rarer still, head-to-head comparison of different γδT cell engineering strategies with the aim of arriving at optimal γδT cell-geared constructs, as opposed to passive adoption of canonical CAR-T strategies optimised for performance in αβT cells.
Similarly, evaluation of γδT cell immunotherapies in combination with therapeutic adjuvants is often restricted to target in vitro pre-treatment with bisphosphonate drugs. The chances of achieving clinical efficacy will be much bolstered by wider evaluation of γδT cell efficacy modulation with checkpoint blockers, mediators of antibody dependent cellular cytotoxicity, chemotherapeutic drugs, radiotherapy and other immunomodulatory agents. The aim of this article collection is to discuss γδT cell immunotherapies for cancer in the context of optimized gene-engineering, and for use in conjunction with translationally relevant combination agents.
This Research Topic is aimed at collecting research articles focused on discussing and evaluating various strategies of improving γδT cell immunotherapeutic efficacy for the treatment of cancer, with a particular interest in optimised gene-engineering and utilisation of combination treatments. We welcome the submission of Original Research, Reviews, Mini Review and Perspective articles to cover the following areas:
• Gene-engineering strategies optimised for use in γδT cells
• Using γδT cells in combination with immunomodulatory drugs
• Boosting γδT cell therapeutic persistence
• γδT cells in combination with chemotherapeutic approaches
• Comparison of different γδT cell engineering modalities
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic editor Dr. Daniel Abate-Daga is an inventor, co-inventor in patents, or co-author of patent applications filed by the Moffitt Cancer Center, including one application involving gamma/delta CAR-T cells. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
γδT cell-based immunotherapies for cancer offer a promising and allo-compatible alternative to classical CAR-αβT approaches, hampered by complex autologous manufacturing logistics and poor efficacy against solid tumor indications. Despite much pre-clinical promise, however, early data from unmodified autologous and allogeneic γδT cell clinical trials of various γδT cell subsets has been largely underwhelming. Data suggests that - much like other adoptive cell therapy substrates - γδT cells too are sensitive to suppression by the tumour microenvironment, functional exhaustion and suffer from a lack of persistence. In the pursuit of transformational γδT cell immunotherapeutic efficacy, it is increasingly apparent that gene-engineering and combination therapies will be indispensable.
As appreciation of the need for gene-engineering and therapeutic combinations grows, the volume of literature evaluating γδT cell engineering strategies and combinations remains low. Direct comparisons between unmodified γδT cells of various subsets and engineered counterparts are rare. Rarer still, head-to-head comparison of different γδT cell engineering strategies with the aim of arriving at optimal γδT cell-geared constructs, as opposed to passive adoption of canonical CAR-T strategies optimised for performance in αβT cells.
Similarly, evaluation of γδT cell immunotherapies in combination with therapeutic adjuvants is often restricted to target in vitro pre-treatment with bisphosphonate drugs. The chances of achieving clinical efficacy will be much bolstered by wider evaluation of γδT cell efficacy modulation with checkpoint blockers, mediators of antibody dependent cellular cytotoxicity, chemotherapeutic drugs, radiotherapy and other immunomodulatory agents. The aim of this article collection is to discuss γδT cell immunotherapies for cancer in the context of optimized gene-engineering, and for use in conjunction with translationally relevant combination agents.
This Research Topic is aimed at collecting research articles focused on discussing and evaluating various strategies of improving γδT cell immunotherapeutic efficacy for the treatment of cancer, with a particular interest in optimised gene-engineering and utilisation of combination treatments. We welcome the submission of Original Research, Reviews, Mini Review and Perspective articles to cover the following areas:
• Gene-engineering strategies optimised for use in γδT cells
• Using γδT cells in combination with immunomodulatory drugs
• Boosting γδT cell therapeutic persistence
• γδT cells in combination with chemotherapeutic approaches
• Comparison of different γδT cell engineering modalities
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Topic editor Dr. Daniel Abate-Daga is an inventor, co-inventor in patents, or co-author of patent applications filed by the Moffitt Cancer Center, including one application involving gamma/delta CAR-T cells. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: γδT Cell Immunotherapy, cancer Immunotherapy, Car-T Cells
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.
