Marpam Pharma LLC

Development of a Treatment for the Durable Remission of Hiv Using Autologous Human Car T Cells That Target B Cell Follicles - 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.