Selected Grantee Publications

A Participant-Derived Xenograft Model of HIV Enables Long-Term Evaluation of Autologous Immunotherapies

McCann et al., Journal of Experimental Medicine. 2021.

https://doi.org/10.1084/jem.20201908

HIV-specific CD8+ T cells partially control viral replication but rarely provide lasting protection due to immune escape. Investigators showed that engrafting NSG mice with memory CD4+ T cells from HIV+ donors enables evaluation of autologous T cell responses while avoiding graft-versus-host disease. Treating HIV-infected mice with clinically relevant T cell products reduced viremia. In vivo activity was significantly enhanced when T cells were engineered with surface-conjugated nanogels carrying an Interleukin-15 superagonist but was ultimately limited by the pervasive selection of escape mutations, recapitulating human patterns. This “participant-derived xenograft” model provides a powerful tool for developing T cell-based therapies for HIV. Supported by ORIP (R01OD011095), NIAID, NIDA, NIMH, NINDS, and NCATS.