?dT cell-based immunotherapies for cancer offer a promising and allo-compatible alternative to classical CAR-aßT 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 ?dT cell clinical trials of various ?dT cell subsets has been largely underwhelming. Data suggests that - much like other adoptive cell therapy substrates - ?dT cells too are sensitive to suppression by the tumour microenvironment, functional exhaustion and suffer from a lack of persistence. In the pursuit of transformational ?dT 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 ?dT cell engineering strategies and combinations remains low. Direct comparisons between unmodified ?dT cells of various subsets and engineered counterparts are rare. Rarer still, head-to-head comparison of different ?dT cell engineering strategies with the aim of arriving at optimal ?dT cell-geared constructs, as opposed to passive adoption of canonical CAR-T strategies optimised for performance in aßT cells.
Similarly, evaluation of ?dT 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 ?dT 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 ?dT 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 ?dT 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 ?dT cells
• Using ?dT cells in combination with immunomodulatory drugs
• Boosting ?dT cell therapeutic persistence
• ?dT cells in combination with chemotherapeutic approaches
• Comparison of different ?dT 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.
?dT cell-based immunotherapies for cancer offer a promising and allo-compatible alternative to classical CAR-aßT 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 ?dT cell clinical trials of various ?dT cell subsets has been largely underwhelming. Data suggests that - much like other adoptive cell therapy substrates - ?dT cells too are sensitive to suppression by the tumour microenvironment, functional exhaustion and suffer from a lack of persistence. In the pursuit of transformational ?dT 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 ?dT cell engineering strategies and combinations remains low. Direct comparisons between unmodified ?dT cells of various subsets and engineered counterparts are rare. Rarer still, head-to-head comparison of different ?dT cell engineering strategies with the aim of arriving at optimal ?dT cell-geared constructs, as opposed to passive adoption of canonical CAR-T strategies optimised for performance in aßT cells.
Similarly, evaluation of ?dT 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 ?dT 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 ?dT 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 ?dT 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 ?dT cells
• Using ?dT cells in combination with immunomodulatory drugs
• Boosting ?dT cell therapeutic persistence
• ?dT cells in combination with chemotherapeutic approaches
• Comparison of different ?dT 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.
