Development of a treatment for the durable remission of HIV using autologous human car t cells that target b cell follicles
Ended Project Grant Awarded Last action
- Award ID
- R42AI155031
- Recipient
-
Marpam Pharma LLC UEI FJN8ZEF912K7
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $5,231,786
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Funding
-
- $4,212,788.94 Federal
- $1,018,997.00 Non-federal
- Place of performance
- Minnesota, USA
Award details come from USAspending.gov.
Description
- Abstract
- Marpam pharma is developing a one-time treatment for durable remission of human immunodeficiency virus (HIV) for patients treated with antiretroviral therapy (art). This treatment is an autologous HIV-specific chimeric antigen receptor (car; specifically, CD4-MBL-car) t cell therapy that employs the CXCR5 chemokine receptor as a homing device to direct anti-HIV killer t cells into "hidden" viral reservoirs located in lymphoid FOLLICLES1,2. B cell follicles are an immune protected site where the majority of viral replication can occur relatively unabated in CD4+ t CELLS3-7, likely due to a markedly lower presence of virus-specific CD8 t cells inside compared to outside of b cell follicles in lymphoid TISSUE8-11. In fact, few virus-specific CD8 t cells express the follicular homing molecule CXCR510, possibly explaining the 40-fold lower in vivo effector CTL to target vrna+ cell levels inside compared to outside of b cell FOLLICLES10. These findings suggest that the inability of HIV-specific CD8 t cells to fully suppress virus replication may be due to a deficiency of virus-specific CD8 t cells in b cell follicles. Importantly, pilot studies of this car-t cell treatment showed safety in animals and also successful homing of car-t cells to b cell follicles, evidence of direct contact of the car-t cells with viral RNA+ infected cells, and decreased viral loads in art-suppressed rhesus macaques infected with simian immunodeficiency virus (SIV), a model of HIV. Here, we propose to conduct an IND-enabling preclinical study to assess the safety and efficacy of autologous car-t cells transduced with the human car construct in a study statistically powered to demonstrate efficacy in a rhesus macaque simian-human immunodeficiency virus (shiv) model of HIV. In our recent sttr phase 1 studies, we successfully produced human car-t cells using a small-scale research method. Here, we propose to develop a scalable method for GMP production of gammaretrovirus and car/CXR5-t cells. These proposed studies will move our product from the current preclinical stage of development into clinical development.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | -$81,327 | $0 | |
| Amendment | $118,524 | $0 | |
| Amendment | $118,524 | $0 | |
| Amendment | $1,009,537 | $0 | |
| Amendment | $1,009,537 | $0 | |
| Amendment | $1,018,997 | $0 | |
| Original award | $1,018,997 | $1,018,997 |
Quick answers
Who received award R42AI155031?
R42AI155031 was awarded to Marpam Pharma LLC by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 18, 2020.
How much is award R42AI155031 worth?
$5,231,786 has been obligated on R42AI155031: $4,212,789 in federal funding and $1,018,997 in non-federal funding.
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