This federal Project Grant award from the National Cancer Institute's Cancer Biology Research program (CFDA 93.396) is providing $1,876,547.00 to New York University School of Medicine to conduct research aimed at optimizing T cell receptor (TCR)-CD3 signaling for cancer immunotherapy. The project will use in vitro methods, structural analysis, and in vivo testing to identify TCR mutations that can enhance immune-mediated tumor killing without losing antigen specificity. The goal is to...
The National Cancer Institute (NCI) awarded a $101,856 Project Grant under the Cancer Research Manpower program (CFDA 93.398) to The Trustees of Columbia University in the City of New York to support research on the impact of genomic variants on T cell anti-tumor activity. The grant funding will enable in-depth mechanistic and in vivo functional studies of single-nucleotide variants in genes like PIK3CD and PPP3CA, which have been found to enhance multiple hallmarks of T cell activity and...
This Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) provides $132,462 to the Fred Hutchinson Cancer Center in Seattle, WA to conduct research aimed at improving engineered T cell receptor (TCR-T) cell therapy for solid tumors. The research seeks to determine why TCR-T cells form a specific stem-like reservoir in tumor-draining lymph nodes, which differs from the reservoir formed by naturally occurring tumor-specific T cells. The project will...
This federal Project Grant award, valued at $154,568 and awarded by the National Cancer Institute (NCI), will support research at Duke University to investigate the role of type 3 innate lymphoid cells (ILC3s) in regulating the melanoma tumor microenvironment. The research aims to enhance understanding of how ILC3s modulate adaptive immune responses, which could inform novel combination treatment strategies to improve the effectiveness of immune checkpoint inhibitor (ICI) therapy for advanced...
This $626,534 federal Project Grant award from the National Cancer Institute's Cancer Biology Research program (CFDA 93.396) supports research by the Medical University of South Carolina (MUSC) to investigate how targeting endoplasmic reticulum (ER) stress and autophagy in T cells can reinvigorate anti-tumor immunity. The research aims to:
Determine how ER stress-induced mitochondrial quality control mechanisms regulate T cell effector function.
Assess how autophagy-induced metabolic changes...
This $460,977 Project Grant award from the National Cancer Institute (NCI) under the Cancer Treatment Research program (CFDA 93.395) supports research to identify novel "chemo-neoepitopes" (CNEs) that can be used as immunogens to mobilize tumor-specific CD8+ T cells for immunotherapy against triple-negative breast cancer (TNBC).
The research, conducted by Health Research, Inc. at the Roswell Park Division, aims to: 1) identify candidate CNE peptide sequences generated by...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $693,880 to the Fred Hutchinson Cancer Center (doing business as Seattle Cancer Care Alliance) to develop a novel cancer immunotherapy approach using engineered CD4+ T cells. The goal is to overcome treatment resistance in solid tumors, such as melanoma, by engineering CD4+ T cells to express IL-12 and IL-18 to activate innate immune cells within the tumor microenvironment. The award...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), aims to investigate the vascular determinants of immune exclusion from the tumor core in melanoma. The $422,971 award, provided to The Trustees of Columbia University in the City of New York, will fund a study to elucidate the development of immune exclusions for different immune cells during melanoma progression and examine the spatial vascular changes in correlation...
This Project Grant award from the National Cancer Institute (CFDA 93.396 - Cancer Biology Research) provides funding of $424,734.00 to the University of Illinois to develop a novel spatial proteomics approach that integrates 3D microscopy techniques with bottom-up proteomic assays. This innovative method will enable deep proteome profiling of specific immune cells located in different subregions of a tumor. The key product will be a workflow to spatially encode and analyze immune cell...
This Project Grant award from the National Cancer Institute (NCI), under the Cancer Treatment Research program (CFDA 93.395), provides $556,711 to Duke University to conduct research on epigenetic programming of T cells for enhanced cellular immunotherapy against cancer. The key objectives are to: 1) prioritize lead epigenetic targets through high-throughput screening of primary human T cells, 2) identify critical transcription factors and regulatory regions governing T cell exhaustion, and...
This $127,049.00 federal Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) aims to define the functional and spatial properties of tumor-specific tumor-infiltrating CD8 T cells. Specifically, the project will:
Generate patient-derived xenograft (PDX) murine models of 3 melanoma patient tumors to test the required diversity of T cell receptors (TCRs) from tumor-infiltrating T cells needed to exert immune pressure on a heterogeneous tumor like melanoma.
Investigate the role of antigen class (neoantigens vs. tumor-associated antigens) in tumor control using one of the melanoma PDX models and a cell-barcoding system to track TCR-specific immune selection.
Utilize spatial sequencing techniques to characterize tumor-intrinsic immunosuppressive interactions and the localization of CD8 T cells within the PDX models, as well as in patient melanoma biopsies.
This research aims to develop a pipeline for isolating and re-expressing putative tumor-specific TCRs in non-exhausted T cells as a potential autologous adoptive cellular therapy for cancer. The award period is from September 1, 2024 to April 30, 2027.