CANCER CELL AND GENE THERAPY (CCGT) PROGRAM PROJECT SUMMARY The goals of the Cancer Cell and Gene Therapy (CCGT) Program are to incorporate advances in cellular and gene therapy into the treatment of cancer. The CCGT Program is a sub-component of the Center for Cell and Gene Therapy and has 21 Research members and 9 Clinical members from multiple departments at BCM, including Medicine, Pediatrics, Surgery, Pathology and Immunology, Molecular and Cell Biology, Neuroscience and Molecular and Human Genetics. The Program received a total of $3.1 million in direct support from the NCI last year and overall received $14.6 million in direct peer-reviewed funding and $23.1 million in total direct funding. In the last 5 years, members of the Program published 412 cancer-related manuscripts in peer-reviewed journals, of which 42% represented intra-programmatic collaborations and 31% inter-programmatic, while 37% included external collaborators and 34% were published in journals with an Impact Factor >10. Our research focuses on three themes: normal and malignant stem cells, adoptive immunotherapy of cancer, and improving outcomes of stem cell transplantation for cancer. CCGT has basic, translational, and clinical research components. Our basic investigators work on understanding the mechanisms by which normal and malignant stem cell growth is controlled, and on the molecular and cellular interactions involved in the development of tumor vasculature and stroma. These researchers are also identifying new targets for immunotherapy, and optimizing presentation of weak tumor antigens to the immune system. Our translational investigators are moving cell- and gene-based therapies from the bench to the bedside in a series of small-scale iterative laboratory- clinical-laboratory protocols, and are also developing pivotal trials. We have a long history of successful and timely implementation of clinical translational projects in gene and cellular therapy, and we have the resources to supply and test all the clinical reagents required, through our clinical research infrastructure and the Cell processing and Vector Production Shared Resource. Major accomplishments in the last 5 years include first-in- man trials of 10 new cell types/constructs and transfer of several strategies to industry for late-phase testing. We have shown activity of virus specific cytotoxic T lymphocytes in virus-associated cancers (resulting in licensure of the approach to three companies for late-phase trials) and in ongoing studies are showing anti-tumor activity of genetically modified T cells in subjects with T cell lymphoma, Hodgkin lymphoma, neuroblastoma, and nasopharyngeal cancer. Our clinical researchers run the adult and (in collaboration with the Pediatric Cancer Program) pediatric hematopoietic stem cell transplant programs and are extending the applicability of transplantation for malignancy by using pre-transplant immunotherapy to enable transplant and post-transplant immunotherapy to augment graft-versus-tumor activity and reconstitute anti-viral immunity. .
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