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Hematology Disease Topics & Pathways:
Chimeric Antigen Receptor (CAR)-T Cell Therapies, Genomics, Biological therapies, Treatment Considerations, Biological Processes, Technology and Procedures
Description:
Gene editing is a novel technology to change specific nucleotides or knockouts in cells, and these are starting to be used clinically. This joint-scientific committee session will include 4 talks that span from basic science to clinical use of gene-edited stem cell products and CAR-T products in malignant and classical hematology.
Dr. Justin Eyquem will discuss his latest work using novel gene editing technologies to improve CAR T-cell function and facilitate their manufacturing. He will present new gene edits associated with improved CAR T-cell functional persistence and novel types of vectors for the generation of CAR T cell in vivo.
Dr. Paulo Rio will present the latest results in optimizing novel genome editing tools, including prime editing, to correct hematopoietic stem cells (HSCs) from Fanconi Anemia (FA) patients. She will discuss the latest advances from her lab in optimizing prime editing technology to efficiently target long-term repopulating HSCs and correct the most common FA mutations in both cell lines and primary HSCs from FA patients.
Dr. Pietro Genovese will present the innovative “epitope editing” strategy for overcoming on-target/off-tumor toxicities in acute myeloid leukemia (AML) immunotherapy. Epitope mapping and library screenings have identified specific amino acid changes that have avoided antibody binding. These have now been introduced into HSPCs via base-editing techniques. Epitope-edited HSPC’s were resistant to CAR-T cell therapy, and enabled specific eradication of patient-derived AML xenografts. Dr. Genovese will discuss the potential of precision immunotherapy for relapsed/refractory AML, non-genotoxic conditioning approaches, and advances in multiplex engineering of HSPCs.
Dr. Julia Skokowa will review recent efforts to establish clinical genome editing to correct severe congenital neutropenia-associated mutations as well as gene editing efforts to inhibit mutated genes in patients' HSCs that may be applicable to other bone marrow failure syndromes. She will also discuss key considerations that are particularly important for gene therapy of pre-leukemic bone marrow syndromes, where gene editing of HSCs should be extremely safe so as not to potentiate the leukemogenic transformation of hematopoiesis. Finally, Dr. Skokowa will present her thoughts on the ethics of gene editing for pre-leukemic bone marrow failure.
Dr. Justin Eyquem will discuss his latest work using novel gene editing technologies to improve CAR T-cell function and facilitate their manufacturing. He will present new gene edits associated with improved CAR T-cell functional persistence and novel types of vectors for the generation of CAR T cell in vivo.
Dr. Paulo Rio will present the latest results in optimizing novel genome editing tools, including prime editing, to correct hematopoietic stem cells (HSCs) from Fanconi Anemia (FA) patients. She will discuss the latest advances from her lab in optimizing prime editing technology to efficiently target long-term repopulating HSCs and correct the most common FA mutations in both cell lines and primary HSCs from FA patients.
Dr. Pietro Genovese will present the innovative “epitope editing” strategy for overcoming on-target/off-tumor toxicities in acute myeloid leukemia (AML) immunotherapy. Epitope mapping and library screenings have identified specific amino acid changes that have avoided antibody binding. These have now been introduced into HSPCs via base-editing techniques. Epitope-edited HSPC’s were resistant to CAR-T cell therapy, and enabled specific eradication of patient-derived AML xenografts. Dr. Genovese will discuss the potential of precision immunotherapy for relapsed/refractory AML, non-genotoxic conditioning approaches, and advances in multiplex engineering of HSPCs.
Dr. Julia Skokowa will review recent efforts to establish clinical genome editing to correct severe congenital neutropenia-associated mutations as well as gene editing efforts to inhibit mutated genes in patients' HSCs that may be applicable to other bone marrow failure syndromes. She will also discuss key considerations that are particularly important for gene therapy of pre-leukemic bone marrow syndromes, where gene editing of HSCs should be extremely safe so as not to potentiate the leukemogenic transformation of hematopoiesis. Finally, Dr. Skokowa will present her thoughts on the ethics of gene editing for pre-leukemic bone marrow failure.