Adoptive immunotherapy with T cells engineered with either a T cell receptor (TCR) or a chimeric antigen receptor (CAR) is driving a New Era of Oncology Immunotherapy. The CAR is an artificial molecule engineered to induce cytolytic T cell reactions in tumor cells. This molecule combines the extracellular single-chain variable fragment (scFv) portion with the ability to recognize epitopes like a monoclonal antibody (mAb) and the intracellular signaling domains that are required for T cells activation. When expressed on T cell surfaces, the CAR enables the recognition and subsequent destruction of cancer cells expressing the complementary antigen on their surface.
At present, the clinical efficacy of TCR T and CAR T cell therapies is limited to specific hematological settings; however, these therapies are beginning to be explored clinically in the treatment of solid tumors. We aim to provide our readers with the latest updates in the field of adoptive ACT with a focus not only on the malignant settings.
The mechanisms of tumor escape are related to host factors affecting CAR-T and TCR-T proliferation and persistence, ACT product features and their toxicity, and tumor-intrinsic factors, like loss of target epitope expression or trogocytosis. This collection will focus on clinical and preclinical results based on ACT. The animal models have been of paramount importance for elucidating the responses to ACT supporting its potential as a curative therapy. In fact, the objective of this collection is, on the one hand, to emphasize the potential of such preclinical models to predict clinical response to ACT and to highlight areas in which research on such models could be improved from lab to the clinic. On the other hand, it will focus on the optimization process aimed at improving efficacy and modulating immunosuppressive elements. This special issue will focus also on the developments and applications of restimulation of antiviral immunity via defined peptides from common pathogens providing a unique therapeutic avenue for cancer immunotherapy (virus-specific T cells) and Oncolytic Viruses (OVs) that have the potential to synergize with adoptive T-cell immunotherapy. This collection will provide an overview of novel insights into the ACT and possible solutions for improving ACT therapy in oncologic and non-oncologic settings.
This Research Topic intends to provide an updated overview of strategy to improve ACT. We welcome the submissions of Original Research, Review, Mini Review, Opinion, Clinical Trial, and Case Report articles covering, but not limited to, the following themes:
• Preclinical and clinical experience: evaluation of responses to Adoptive Cellular Therapies in solid and hematology tumors.
• Gene editing to improve adoptive cellular therapies.
• Transduction/transfection tools in the era of ACT evolution from low to large usage.
• Ex vivo/in vivo models of Adoptive Cellular Therapies studies.
• The role of microenvironment to modulate the ACT
• Novel high-throughput approaches to study Adoptive Cellular Therapies at single cell level
• Novel applications of CAR Ts in non-oncologic setting
• Accelerating ACT with OVs.
• The role of virus to optimize ACT (from virus-specific T cells to viral vaccination to modulate effector cells)
Note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by in vitro or in vivo functional validation are considered out of scope of this section.
Topic Editor Franco Locatelli is Advisory board for Amgen, Neovii, Novartis, Sanofi, Miltenyi, Medac, Gilead, Takeda, Bluebird bio, SOBI, Jazz Pharmaceuticals and Pfizer. The other Topic Editors declare no competing interests.
Adoptive immunotherapy with T cells engineered with either a T cell receptor (TCR) or a chimeric antigen receptor (CAR) is driving a New Era of Oncology Immunotherapy. The CAR is an artificial molecule engineered to induce cytolytic T cell reactions in tumor cells. This molecule combines the extracellular single-chain variable fragment (scFv) portion with the ability to recognize epitopes like a monoclonal antibody (mAb) and the intracellular signaling domains that are required for T cells activation. When expressed on T cell surfaces, the CAR enables the recognition and subsequent destruction of cancer cells expressing the complementary antigen on their surface.
At present, the clinical efficacy of TCR T and CAR T cell therapies is limited to specific hematological settings; however, these therapies are beginning to be explored clinically in the treatment of solid tumors. We aim to provide our readers with the latest updates in the field of adoptive ACT with a focus not only on the malignant settings.
The mechanisms of tumor escape are related to host factors affecting CAR-T and TCR-T proliferation and persistence, ACT product features and their toxicity, and tumor-intrinsic factors, like loss of target epitope expression or trogocytosis. This collection will focus on clinical and preclinical results based on ACT. The animal models have been of paramount importance for elucidating the responses to ACT supporting its potential as a curative therapy. In fact, the objective of this collection is, on the one hand, to emphasize the potential of such preclinical models to predict clinical response to ACT and to highlight areas in which research on such models could be improved from lab to the clinic. On the other hand, it will focus on the optimization process aimed at improving efficacy and modulating immunosuppressive elements. This special issue will focus also on the developments and applications of restimulation of antiviral immunity via defined peptides from common pathogens providing a unique therapeutic avenue for cancer immunotherapy (virus-specific T cells) and Oncolytic Viruses (OVs) that have the potential to synergize with adoptive T-cell immunotherapy. This collection will provide an overview of novel insights into the ACT and possible solutions for improving ACT therapy in oncologic and non-oncologic settings.
This Research Topic intends to provide an updated overview of strategy to improve ACT. We welcome the submissions of Original Research, Review, Mini Review, Opinion, Clinical Trial, and Case Report articles covering, but not limited to, the following themes:
• Preclinical and clinical experience: evaluation of responses to Adoptive Cellular Therapies in solid and hematology tumors.
• Gene editing to improve adoptive cellular therapies.
• Transduction/transfection tools in the era of ACT evolution from low to large usage.
• Ex vivo/in vivo models of Adoptive Cellular Therapies studies.
• The role of microenvironment to modulate the ACT
• Novel high-throughput approaches to study Adoptive Cellular Therapies at single cell level
• Novel applications of CAR Ts in non-oncologic setting
• Accelerating ACT with OVs.
• The role of virus to optimize ACT (from virus-specific T cells to viral vaccination to modulate effector cells)
Note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by in vitro or in vivo functional validation are considered out of scope of this section.
Topic Editor Franco Locatelli is Advisory board for Amgen, Neovii, Novartis, Sanofi, Miltenyi, Medac, Gilead, Takeda, Bluebird bio, SOBI, Jazz Pharmaceuticals and Pfizer. The other Topic Editors declare no competing interests.