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Description:
This scientific session will highlight innovative translational strategies that leverage genome engineering to inform fundamental mechanisms to enhance cancer immunity or overcome clinical challenges of classical CAR T cell therapies.
Dr. Carl June will discuss three genome engineering approaches to improve CAR T cell responses. The first explores CRISPR-Cas9-mediated deletion of co-inhibitory CTLA4 in CAR T cells. The second seeks to develop a universal therapy for hematologic malignancies by targeting the pan-leukocyte marker CD45, protected from on-target/off-tumor toxicity through CRISPR adenine base editing. The third addresses the issue of loss of inflammatory effector functions in T cell therapies, including knock out of both Regnase-1 and Roquin-1.
Dr. Chiara Bonini will discuss how the development of genetic engineering technologies (CAR, transgenic tumor reactive TCR) and genome editing tools have dramatically changed and expanded the landscape of adoptive cellular therapy. This includes both expanding opportunities and new questions: how to isolate, design, and combine tools to generate the most fit engineered T cells to treat malignant diseases. Optimal strategies will allow immune cells to infiltrate and survive in the tumor microenvironment, recognize relevant tumor antigens, and to persist as memory cells.
Dr. Dan Kaufman will discuss strategies to utilize natural killer (NK) cells and macrophages to target refractory malignancies. NK cells isolated or derived from peripheral blood, umbilical cord blood or induced pluripotent stem cells (iPSCs) can be engineered to express CARs and modified to improve their anti-tumor activity. Specific approaches include deletion of CISH and TGFbII receptor, or engineered resistance to immunosuppressive drugs. These NK cell and macrophage cellular therapies enable new strategies to enhance innate immune responses to cancer.
Dr. Alexander Marson will discuss using CRISPR-mediated gene editing in primary human T cells to systematically identify genetic targets that modulate the functions of T cells in contexts ranging from immunosuppression to cancer killing. Development and application of CRISPR-based methodologies such as pooled knock-in screening, CRISPR activation, and CRISPR interference pinpoint the regulatory networks controlling T cell phenotypes and identify synthetic genetic programs to improve T cell activity in cancer, autoimmunity, and infection.
Dr. Carl June will discuss three genome engineering approaches to improve CAR T cell responses. The first explores CRISPR-Cas9-mediated deletion of co-inhibitory CTLA4 in CAR T cells. The second seeks to develop a universal therapy for hematologic malignancies by targeting the pan-leukocyte marker CD45, protected from on-target/off-tumor toxicity through CRISPR adenine base editing. The third addresses the issue of loss of inflammatory effector functions in T cell therapies, including knock out of both Regnase-1 and Roquin-1.
Dr. Chiara Bonini will discuss how the development of genetic engineering technologies (CAR, transgenic tumor reactive TCR) and genome editing tools have dramatically changed and expanded the landscape of adoptive cellular therapy. This includes both expanding opportunities and new questions: how to isolate, design, and combine tools to generate the most fit engineered T cells to treat malignant diseases. Optimal strategies will allow immune cells to infiltrate and survive in the tumor microenvironment, recognize relevant tumor antigens, and to persist as memory cells.
Dr. Dan Kaufman will discuss strategies to utilize natural killer (NK) cells and macrophages to target refractory malignancies. NK cells isolated or derived from peripheral blood, umbilical cord blood or induced pluripotent stem cells (iPSCs) can be engineered to express CARs and modified to improve their anti-tumor activity. Specific approaches include deletion of CISH and TGFbII receptor, or engineered resistance to immunosuppressive drugs. These NK cell and macrophage cellular therapies enable new strategies to enhance innate immune responses to cancer.
Dr. Alexander Marson will discuss using CRISPR-mediated gene editing in primary human T cells to systematically identify genetic targets that modulate the functions of T cells in contexts ranging from immunosuppression to cancer killing. Development and application of CRISPR-based methodologies such as pooled knock-in screening, CRISPR activation, and CRISPR interference pinpoint the regulatory networks controlling T cell phenotypes and identify synthetic genetic programs to improve T cell activity in cancer, autoimmunity, and infection.