Genetic engineering of T cells with chimeric antigen receptors facilitates the target-specific activation of immune cells against tumor cells. Given their impressive efficiency, especially in treatment of CD19+ B cell malignancies, CAR-T cells are becoming an increasingly important pillar in everyday clinical practice. To date, 5 different CAR-T cell products have been launched on the American and European markets. However, CAR-T cells still face several bottlenecks when translating to other haematological malignancies or solid tumors. These include e.g. the lack of unique target antigens, poor CAR T cell trafficking, local immunosuppression and development of antigen-escape variants. Beyond this, efforts are also being made to overcome general limitations such as CAR-T cell persistence and lack of control mechanisms. Recent advances in CAR-T cell development are tackling these problems by offering novel solutions to increase specificity/efficiency and reduce the risk of side effects such as controllable adapter CAR platforms, suicide switches, dual CARs, gated CARs and novel combinations of CAR therapies with standard therapies e.g. small molecules, radiotherapy and/or chemotherapy.In this Research Topic, we aim to collect articles on basic and translational research addressing emerging strategies to overcome current roadblocks in CAR-T cell immunotherapy. This Research Topic accepts Original Research, Methods, Review and Mini-Review, Clinical Trial, Perspective, Case Report, and Brief Research Reports. We welcome manuscripts focusing on, but not limited to, the following sub-topics:• Adapter CAR-T cells• Novel CAR immune cells (NK, macrophages etc.) • Overcoming the immunosuppressive tumor microenvironment • Tackling the stem cell niche• Improving CAR-T cell trafficking and tumor infiltration• Novel combinations of CAR-T cell therapy and radio-/chemotherapy• Combining CAR-T cells with other treatment modalities (e.g. small molecules,…)• Combinatorial and gated targetingManuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.
Genetic engineering of T cells with chimeric antigen receptors facilitates the target-specific activation of immune cells against tumor cells. Given their impressive efficiency, especially in treatment of CD19+ B cell malignancies, CAR-T cells are becoming an increasingly important pillar in everyday clinical practice. To date, 5 different CAR-T cell products have been launched on the American and European markets. However, CAR-T cells still face several bottlenecks when translating to other haematological malignancies or solid tumors. These include e.g. the lack of unique target antigens, poor CAR T cell trafficking, local immunosuppression and development of antigen-escape variants. Beyond this, efforts are also being made to overcome general limitations such as CAR-T cell persistence and lack of control mechanisms. Recent advances in CAR-T cell development are tackling these problems by offering novel solutions to increase specificity/efficiency and reduce the risk of side effects such as controllable adapter CAR platforms, suicide switches, dual CARs, gated CARs and novel combinations of CAR therapies with standard therapies e.g. small molecules, radiotherapy and/or chemotherapy.In this Research Topic, we aim to collect articles on basic and translational research addressing emerging strategies to overcome current roadblocks in CAR-T cell immunotherapy. This Research Topic accepts Original Research, Methods, Review and Mini-Review, Clinical Trial, Perspective, Case Report, and Brief Research Reports. We welcome manuscripts focusing on, but not limited to, the following sub-topics:• Adapter CAR-T cells• Novel CAR immune cells (NK, macrophages etc.) • Overcoming the immunosuppressive tumor microenvironment • Tackling the stem cell niche• Improving CAR-T cell trafficking and tumor infiltration• Novel combinations of CAR-T cell therapy and radio-/chemotherapy• Combining CAR-T cells with other treatment modalities (e.g. small molecules,…)• Combinatorial and gated targetingManuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.