Interrogating and enhancing endogenous priming of engineered T cells for superior anti-tumor efficacy
Active Project Grant Awarded Last action
- Award ID
- F30CA314103
- Recipient
-
The Leland Stanford Junior University UEI HJD6G4D6TJY5
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $43,373
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date 0% complete
- Place of performance
- Palo Alto, CA 94305, USA
Award details come from USAspending.gov.
Description
- Abstract
- Adoptive T cell therapies, particularly those engineered with tumor-specific T cell receptors (TCR-T), represent a promising approach for cancer treatment. Despite recent advancements, a significant number of patients do not achieve durable responses, underscoring the need for improved strategies to sustain robust anti-tumor activity. Current TCR-T cell approaches do not fully utilize the potential of endogenous antigen-presenting cells (APCS) to enhance and sustain therapeutic efficacy. Additionally, lymphodepleting chemotherapy which is often used to facilitate T cell engraftment, can impair the function of these critical immune cells. This research aims to identify host APC subsets that interact with and sustain TCR-T cells in lymphoreplete hosts, and to optimize T cell-intrinsic signaling pathways to enhance these interactions. IT is hypothesized that APC subsets beyond type 1 conventional dendritic cells (CDC1S) play a crucial role in supporting TCR-T cell efficacy, and that modulating JAK/stat signaling within TCR-T cells will improve their interactions with APCS and enhance antitumor responses. Aim 1 involves delineating the host APC subsets that functionally interact with engineered TCR-T cells. This will be achieved by characterizing TCR-T cells in proximity to host MHC-I+ subsets in tumor-draining lymph nodes and assessing the functional role of CDC1S and other APC subsets using genetic mouse models. Aim 2 focuses on optimizing the CO-localization of TCR-T cells and APCS to maximize T cell expansion, persistence, and antitumor efficacy. This includes examining the effects of TCR-T cell-intrinsic JAK/stat signaling alterations on their interactions with host APCS and assessing the combined efficacy of TCR-T cells and mrna-LNP antigen delivery. The study aims to provide insights into the cellular interactions that sustain TCR-T cell efficacy and inform future combination therapy strategies that leverage emerging antigen delivery systems and TCR-T cell signals. Conducted at stanford university school of medicine, the research is supported by a multidisciplinary team with expertise from DR. Anusha kalbasi and DR. Christopher garcia. Their combined knowledge in immunology, cancer therapy, and protein engineering provides a comprehensive approach to advancing TCR-T cell therapies, aiming to improve their efficacy and accessibility for cancer treatment.
Quick answers
Who received award F30CA314103?
F30CA314103 was awarded to The Leland Stanford Junior University by National Cancer Institute (National Institutes of Health) on December 1, 2026.
How much is award F30CA314103 worth?
$43,373 has been obligated on F30CA314103.
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