P01CA247886

Transforming Human Pancreatic Cancer into an Immunologic Disease - Pancreatic Ductal Adenocarcinoma (PDA) is rising in incidence but remains deadly for most patients. Some progress has occurred in activating immune responses against PDA; however, there are unanswered questions that need to be addressed for immunotherapy to have a significant impact on the lives of PDA patients.

Our team will address two critical problems: 1) inefficient generation of high-quality T cells targeted against PDA antigens capable of tumor trafficking and killing; and 2) multiple cellular barriers that comprise stromal and myeloid cells that inhibit effector T cell trafficking and function in the PDA tumor microenvironment (TME).

Both clinical studies ("science in patients") and pre-clinical studies (mouse models) will be conducted to address these issues and to evaluate novel combinatorial therapies that successfully modulate PDA stroma and chronic inflammation to facilitate improved tumor infiltration of high-quality and durable cancer-targeted T cells.

This program is composed of 4 projects and 4 cores. The four projects will address the common overarching theme that PDA is composed of multiple cell types and signals that inhibit T cell induction, trafficking into, and function in tumors. Each project will address either the induction of quality T cells or the modulation of suppressive cell populations as major barriers to T cell infiltration and activation, and all will integrate agents that bypass these suppressive mechanisms with optimal T cell therapies.

Projects 1, 2, and 4 will combine ongoing preclinical studies aimed at uncovering mechanisms of suppression of different barriers with translational clinical trials that study combination therapy to bypass these suppressive mechanisms. Project 3 will conduct a biomarker-heavy clinical trial using a multi-arm platform design that will add and delete immune modulatory arms based on data from biomarker analysis in this project and from data that feeds into this project from the other 3 projects.

Standard procedures will be used across projects to collect and bank serial biospecimens obtained from patients treated on the clinical trials. The cores will be critical for conducting the proposed assays and for analysis and integration of the data. A program database will be developed to allow for integration of data generated from these assays across the entire program. This will be a unique database that will also bring in data from other sources such as the TCGA database and will provide the program team with the ability to compare results based on the genetics and inflammatory composition of each patient's tumor and their response to the therapy they received.

The final outcomes will include results from a number of therapeutic interventions, approaches to optimize each therapeutic, the potential to further integrate therapies that were tested in one or more projects in future trials, and the ability to develop TME signatures that may further stratify patients for therapeutic interventions. This program will substantially accelerate progress in PDA therapy and allow otherwise nearly impossible achievements in defining predictors of successful immunological therapeutic intervention for PDAs.

The Johns Hopkins University

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

Baltimore, Maryland 212051832 United States

Single Zip Code

National Cancer Institute Program Project Applications (P01 Clinical Trial Optional) (PAR-20-077)

Amendment Since initial award the total obligations have increased 391% from $2,582,338 to $12,679,276.