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G - Cell Therapies -> Cell Therapies (Includes development of somatic, embryonic and induced pluripotent stem cells or other therapeutic cell populations, and issues related to cell expansion or processing)

Chimeric Antigen Receptor (CAR)-Modified Stem Cells Generate Superior Anti-HIV Efficacy Compared to CAR-Modified Autologous Peripheral T Cells in Preclinical Animal Models

Type: Oral Abstract Session

Presentation Details
Session Title: Late-breaking Abstracts 2
Location: Concourse Hall 152 & 153
Start Time: 5/19/2023 10:15
End Time: 5/19/2023 10:30

Therapeutic strategies utilizing chimeric antigen receptors (CARs) against HIV are an area of focus in the development of a functional cure. However, one of the major limitations of T cell-based CAR therapy against HIV is the lack of in vivo persistence, which results in minimal clinical efficacy. In our studies using the humanized bone marrow/liver/thymus (BLT) mouse model and nonhuman primate model (NHP) of HIV infection, we compared two CAR-based gene therapy approaches: one using a classical adoptive T cell approach and one using a stem cell-based approach. In our adoptive T cell approach, we attempted to optimize this strategy to generate greater persistence of autologous anti-HIV CAR+ T cells after infusion in infected animals. In our stem-cell based approach, we modified CD34+ hematopoietic stem cells (HSCs) with anti-HIV CAR vector to generate humanized mice and NHP animals reconstituted with stem-cell derived CAR T cells followed by HIV or SHIV infection. In both approaches, the antiviral effects, cellular persistence, and cellular function were monitored and compared. Our results show that in an adoptive peripheral T cell-based CAR approach, limited in vivo persistence and expansion of autologous anti-HIV CAR T cells was observed in both animal models. This led to minimal control of plasma viral load. In contrast, in our HSC-based CAR approach, we observed sustained CAR-expressing T cell expansion following infection in both animal models. In addition, stem cell derived CAR T cells had a significant, sustained impact on viral loads. Our results using both small and large animal models of HIV infection strongly suggest that a stem cell-based CAR T cell approach may be more optimal to generate long term persistence and antiviral responses against HIV infection.

Mayra A. Carrillo1, Anjie Zhen1, Christopher Peterson2, William Mu1, Valerie Rezek1, Heather Martin1, Hans-Peter Kiem3, Scott G. Kitchen4

1UCLA, Los Angeles, CA,2University of Washington, Seattle, WA,3Fred Hutch, Seattle, WA,4David Geffen School of Medicine at UCLA, Los Angeles, CA
 M.A. Carrillo: None.

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