A participant-derived xenograft model of HIV enables long-term evaluation of autologous immunotherapies. Academic Article uri icon

Overview

abstract

  • HIV-specific CD8+ T cells partially control viral replication and delay disease progression, but they rarely provide lasting protection, largely due to immune escape. Here, we show that engrafting mice with memory CD4+ T cells from HIV+ donors uniquely allows for the in vivo evaluation of autologous T cell responses while avoiding graft-versus-host disease and the need for human fetal tissues that limit other models. Treating HIV-infected mice with clinically relevant HIV-specific T cell products resulted in substantial reductions in viremia. In vivo activity was significantly enhanced when T cells were engineered with surface-conjugated nanogels carrying an IL-15 superagonist, but it was ultimately limited by the pervasive selection of a diverse array of escape mutations, recapitulating patterns seen in humans. By applying mathematical modeling, we show that the kinetics of the CD8+ T cell response have a profound impact on the emergence and persistence of escape mutations. This "participant-derived xenograft" model of HIV provides a powerful tool for studying HIV-specific immunological responses and facilitating the development of effective cell-based therapies.

publication date

  • May 14, 2021

Research

keywords

  • HIV Infections
  • HIV-1
  • Heterografts

Identity

PubMed Central ID

  • PMC8129803

Scopus Document Identifier

  • 85106548533

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2018.00140

PubMed ID

  • 33988715

Additional Document Info

volume

  • 218

issue

  • 7