Marpam Pharma LLC

Proof of Concept Studies for in Vivo Produced Car-t Cells That Target B Cell Follicles as a Treatment for Hiv - Abstract Marpam Pharma Is Developing a Chimeric Antigen Receptor (car)-t Cell Treatment That Targets Viral Reservoirs for Durable Remission of Hiv Without the Need for Antiretroviral Therapies (art). This Treatment Is an Hiv-specific 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 in B Cell Follicles of Secondary Lymphoid Tissue, So That They Can Kill Hiv-producing Cells Where the Majority of Viral Replication Occurs. Using the Best in Vivo Nonhuman Primate (NHP) Model of Hiv, We Developed CAR/CXCR5-T Cells That Show Successful Homing to B Cell Follicles, Evidence of Direct Contact With Viral Rna+ Infected Cells, Markedly Decreased Virus in B Cell Follicles, and Decreased Viral Loads in CAR/CXCR5-T Cell Treated Art-suppressed Simian Immunodeficiency Virus- Infected NHPS Compared to Controls. Our Human CAR/CXCR5-T Cells Also Show CXCR5-DRIVEN Migratory and Anti-hiv Killing Characteristics in Vitro, Showing Promise as a Treatment for People Living With Hiv. Fda-approved Car-t Cell Therapies Are Successful in Treating Various Cancers; However, the Processes to Produce the Car- T Cells Are Complex, Involving Leukapheresis and Ex-vivo Manipulation of Peripheral Blood Mononuclear Cells Prior to Reinfusion Back to the Patient. Thus, Recent Efforts Are Focused on Developing Universal, Off-the-shelf in Vivo-produced Car-t Cell Therapies, Including the Use of Adeno-associated Virus (AAV) Gene Delivery Systems. Since the Process to Produce an Off-the-shelf Aav Gene Therapy Is a Fraction of the Complexity of Ex-vivo Production of Car-t Cells Individualized for Each Patient, the Expectation Is That Aav Gene Therapy to Produce CAR/CXCR5-T Cells Will Eventually Prove to Be Less Costly Than Current Life-long Therapy for Hiv, Which Is Estimated at Over $500,000. to Develop an Off-the-shelf in Vivo CAR/CXCR5-T Cell Product, This Proposal Seeks to Perform the Necessary First Steps of Producing Receptor-targeted, Aav-directed Car-t Cells (second Generation [2G] -CAR/CXCR5-T Cells) in Vitro and Assessing Their Targeted Efficacy Against Hiv. Using Our Intellectual Property-protected Technology to Assemble Aav Composites for Receptor-targeted Gene Delivery, We Propose in Vitro Proof-of-concept Studies to Produce Receptor-targeted, Aav-directed 2G-CAR/CXCR5-T Cells Using Aav Composites Containing ANTI-CD5 Monoclonal Antibody (CD5MAB) and Carrying a 2G-CAR/CXCR5 Dna Payload. as T Cells Specifically Express CD5 on Their Cell Surface, AAV-CD5MAB Composites Carrying 2G- CAR/CXCR5 Dna Payload (AAV-CD5MAB-2G-CAR/CXCR5) Are Expected to Specifically Bind CD5 on T Cells and Transduce Them, Thereby Producing Functional 2G-CAR/CXCR5-T Cells That Home to B Cell Follicles in Vivo. Successful Completion of the Proposed Studies Will Lay the Groundwork Not Only for Phase Ii Ind-enabling Studies for in Vivo Hiv 2G-CAR/CXCR5-T Cells, But Also for Other Therapeutic Areas That Could Benefit From Off-the-shelf in Vivo Production of Car-t Cells.