About this Research Topic
Adoptive cellular immunotherapy of cancer, particularly chimeric antigen receptor-transduced T cell (CAR-T) therapies, have enjoyed an explosion of clinical trials and translational and basic research in the past decade.
The concept and design of the CAR, though originally intended to optimize targeting of innate natural killer cells (NK cells) to tumor-specific antigens, was laterally applied in the past decade to conventional autologous and later third-party allogeneic T cells with first-in-kind successes in leukemia immunotherapy in both adults and children. This approach also spawned the development of an entire industry focused on cancer immunotherapy, laying the foundation for the current paradigm shifts away from toxic chemo/radiotherapy to immune targeting. Aside from cytokine-release toxicities, specific obstacles plaguing existing CAR-T cell therapies include suboptimal killing by fatigued or senescent autologous patient-derived T cells derived, acquisition of tumor resistance to T-cell based immune therapies, and graft-versus-host disease (GVHD) associated with allogeneic conventional T cell therapies.
Innate immune therapies share several immunologically sound potential advantages over current therapies with respect to these ongoing challenges in the field. Their lack of MHC restriction in most primary effector functions render them able to function well across HLA barriers when derived from healthy (related or unrelated) donors, thereby bypassing the potential functional defects acquired through cancer treatment and/or immunosuppression in cancer patients who have been heavily pretreated with chemo/radiotherapy and/or hematopoietic cell transplantation (HCT). Salient differences in regulation mechanisms in innate versus adaptive cells allow robust innate immune killing function of relapsed tumors and prevent or regulate GVHD or off-target inflammation, including reducing the risk for cytokine release syndromes seen with conventional CAR-T cell therapies. Owing both to their frequency in peripheral blood sources as well as the lack of HLA restriction, innate immune subsets are generally more easily expandable to the numbers required for effective cancer immunotherapy. Finally, the lack of HLA restriction allows off-the-shelf (third party healthy donor) immunotherapy as a portable and more cost-effective option globally as compared to adaptive immunotherapies.
This Research Topic aims to provide a rigorous overview of basic mechanisms and translational and clinical advances in the design, development, and deployment of innate immune therapies for cancer. The topic will span both allogeneic and autologous cell product sources, in some articles delving into the relevant nuances in clinical advantages between these. We welcome the submission of Original Research, Review, Mini-Review, Clinical Trial, and Perspective articles including, but not limited to:
1. Preclinical and clinical experience using innate immune therapies against adult and pediatric malignancies
2. Novel processing, manufacturing, and gene editing strategies to improve the efficacy and safety of innate
immune therapies for cancer in the non-transplant or peri-transplant setting
3. Storage, preservation, and retrieval considerations in innate immune therapies
4. Considerations in the choice of optimal immune subsets and donor sources (related, unrelated) for innate
immunotherapy of adult and/or pediatric cancer
5. Immune monitoring of therapies and disease burden with special considerations in monitoring innate immune
therapies
6. Mechanisms of tumor immune escape and potential future directions to address this using innate immune
therapies
Topic Editor Rizwan Romee received financial support from CRISPR Therapeutics. The other Topic Editor declares no competing interests with regard to the Research Topic subject.
The concept and design of the CAR, though originally intended to optimize targeting of innate natural killer cells (NK cells) to tumor-specific antigens, was laterally applied in the past decade to conventional autologous and later third-party allogeneic T cells with first-in-kind successes in leukemia immunotherapy in both adults and children. This approach also spawned the development of an entire industry focused on cancer immunotherapy, laying the foundation for the current paradigm shifts away from toxic chemo/radiotherapy to immune targeting. Aside from cytokine-release toxicities, specific obstacles plaguing existing CAR-T cell therapies include suboptimal killing by fatigued or senescent autologous patient-derived T cells derived, acquisition of tumor resistance to T-cell based immune therapies, and graft-versus-host disease (GVHD) associated with allogeneic conventional T cell therapies.
Innate immune therapies share several immunologically sound potential advantages over current therapies with respect to these ongoing challenges in the field. Their lack of MHC restriction in most primary effector functions render them able to function well across HLA barriers when derived from healthy (related or unrelated) donors, thereby bypassing the potential functional defects acquired through cancer treatment and/or immunosuppression in cancer patients who have been heavily pretreated with chemo/radiotherapy and/or hematopoietic cell transplantation (HCT). Salient differences in regulation mechanisms in innate versus adaptive cells allow robust innate immune killing function of relapsed tumors and prevent or regulate GVHD or off-target inflammation, including reducing the risk for cytokine release syndromes seen with conventional CAR-T cell therapies. Owing both to their frequency in peripheral blood sources as well as the lack of HLA restriction, innate immune subsets are generally more easily expandable to the numbers required for effective cancer immunotherapy. Finally, the lack of HLA restriction allows off-the-shelf (third party healthy donor) immunotherapy as a portable and more cost-effective option globally as compared to adaptive immunotherapies.
This Research Topic aims to provide a rigorous overview of basic mechanisms and translational and clinical advances in the design, development, and deployment of innate immune therapies for cancer. The topic will span both allogeneic and autologous cell product sources, in some articles delving into the relevant nuances in clinical advantages between these. We welcome the submission of Original Research, Review, Mini-Review, Clinical Trial, and Perspective articles including, but not limited to:
1. Preclinical and clinical experience using innate immune therapies against adult and pediatric malignancies
2. Novel processing, manufacturing, and gene editing strategies to improve the efficacy and safety of innate
immune therapies for cancer in the non-transplant or peri-transplant setting
3. Storage, preservation, and retrieval considerations in innate immune therapies
4. Considerations in the choice of optimal immune subsets and donor sources (related, unrelated) for innate
immunotherapy of adult and/or pediatric cancer
5. Immune monitoring of therapies and disease burden with special considerations in monitoring innate immune
therapies
6. Mechanisms of tumor immune escape and potential future directions to address this using innate immune
therapies
Topic Editor Rizwan Romee received financial support from CRISPR Therapeutics. The other Topic Editor declares no competing interests with regard to the Research Topic subject.
Keywords: Innate Immunity, cell therapy, off-the-shelf, allogeneic, autologous, immune escape
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.
