Development of CD4 TCR-engineered t cell immunotherapy in triple-negative breast cancer
Active Project Grant Awarded Last action
- Award ID
- R44CA295183
- Recipient
-
Immunova Therapeutics LLC UEI J8RSMABQPN95
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,000,000
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date 71% complete
- Originally
- Place of performance
- Monrovia, CA 91016, USA
Award details come from USAspending.gov.
Description
- Abstract
- Breast cancer is a leading cause of cancer-related deaths of women in the united states and worldwide. Immunotherapy is a promising approach, but has not proven successful yet in metastatic breast cancer, particularly in triple-negative breast cancer (tnbc). Tnbc is the most aggressive subtype among all breast cancer subtypes, with little treatment options available. First-line treatment with pembrolizumab-chemotherapy results in better overall survival than chemotherapy alone among patients with advanced tnbc. Sacituzumab govitecan is offered as an option for the second line of treatment. Despite these significant progresses, most patients eventually collapse and DIE without further treatment option. Thus, tnbc remains an unmet medical need for urgent development of novel therapeutics. The rationale for this application is that clinical responses to immune checkpoint therapy rely on the presence of tumor-infiltrating and antigen-specific t cells. Thus, development of tumor-specific TCR-t cell immunotherapy is key to the success of immunotherapy in breast cancer. Immunova therapeutics is a startup company with the mission to further develop TCR-t cell immunotherapy for the treatment of solid cancers, including tnbc. Due to the nature of tumor heterogeneity, antigen loss or negative tumor variants represents a key mechanism to develop resistance to immunotherapy. This IMT-422 product is an HLA-DR13- restricted KK-LC-1-specific TCR-engineered CD4+ t cells, and has been demonstrated to completely inhibit or even eliminate tnbc in a mouse model. Our finding is also supported by recent studies showing that CD4+ t cells could eliminate antigen-positive and -negative tumor cells. To further improve the therapeutic potential, we engineered TCR with three key technologies to increase the pools of stem-like memory t cells and resistance to t cell exhaustion and immune suppression. We named the final IMT-422 product as CD4 TCR-stem t cells, which could completely reject breast cancer growth in a mouse model. Based on these solid data, we propose to generate GMP grade master cell bank (MCB) and viral particles of TCR-stem required for chemistry, manufacturing and controls (CMC) (aim 1); and determine the pharmacokinetics, biodistribution and pharmacological toxicity of the IMT-422 (CD4 TCR-stem t cells) product (aim 2). Upon completion of the proposed studies, we are well positioned to initiate and file an investigator-initiated new drug (IND) application for a future phase i clinical trial, thus accelerating the development of new breast cancer immunotherapy.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $998,971 | |
| Original award | $1,001,029 |
Quick answers
Who received award R44CA295183?
R44CA295183 was awarded to Immunova Therapeutics LLC by National Cancer Institute (National Institutes of Health) on September 20, 2024.
How much is award R44CA295183 worth?
$2,000,000 has been obligated on R44CA295183.
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