CORE SUPPORT FOR THE IMMUNE CELL NETWORK

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The engineering of autologous or allogenic cells for clinical application has accelerated in recent years, to a point where significant successes have been observed with treatments for cancer and tissue damage from radiation and chemotherapy. Many cell types may be utilized including hematopoietic stem cells, induced pluripotent stem cells (iPSC), lymphocytes, dendritic cells, mesenchymal stem cells, and others. Cell-based immunotherapies have been particularly successful. There are approved agents for hematologic malignancies such as leukemia, lymphoma and myeloma; promising work is also being conducted to treat solid tumors. However, there remain significant scientific, technical, clinical, and regulatory challenges to bringing this powerful therapeutic strategy into widespread, effective clinical use. Investigators are just beginning to develop constructs that effectively destroy tumors while preserving normal tissue. Technical challenges include the complex manufacturing process used to make patient-specific final products from unique patient-specific starting materials or allogenic products that do not trigger an immune rejection. Standardized analytical assays must be developed to fully characterize cell products before and after these ‘living drugs’ are administered to patients and animal model studies may not be predictive. Furthermore, many therapeutic indications are for rare cancers or for those subtypes with small number of patients making it impossible to accrue statistically significant trial subjects at a single clinical site. As cell therapy science advances, there must also be an associated advancement in regulatory science to ensure that both quality and safety conform to the highest standards. Currently, no single institution is equipped to address all the hurdles that exist in the cell therapy field. The NCI seeks to provide core support for members of an Immune Cell Network (ICN). The ICN will consist of NIH-funded Centers that foster new discoveries, support strong collaborations across scientific, clinical, and regulatory disciplines, and make their own resources available across the network to advance the application of cell therapies produced under cGMP conditions for clinical trials. Each center will conduct research on one or more cancers using an adoptive cell therapy approach. The research consists of selecting a credentialed target for a specific cancer, interrogating therapeutic mechanism(s) of action, determining therapeutic cell fitness and persistence, and assessing clinical efficacy in human trials of novel cell therapy products. Specific cellular therapies supported may include immunotherapies [chimeric antigen receptor (CAR) T-cells, tumor-infiltrating lymphocytes (TIL), engineered T cell receptor (TCR)-T cells, natural killer (NK), dendritic cell (DC), and macrophage (MΦ)]; stem cell therapies (engineered iPSC, tissue stem cells, hematopoietic progenitors); and paracrine-acting cells (engineered mesenchymal cells). The centers will manufacture cell therapy products onsite for their own pilot trials and collaborate scientifically in multisite clinical studies to bring forward the most innovative ideas rapidly.