Project Details
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.
Status | Finished |
---|---|
Effective start/end date | 8/9/21 → 7/31/23 |
Funding
- National Institute of Allergy and Infectious Diseases: $118,524.00
- National Institute of Allergy and Infectious Diseases: $1,009,537.00
- National Institute of Allergy and Infectious Diseases: $1,018,997.00
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