# Characterization of a Memory CD4+ T-cell Humanized Mouse Model for the Evaluation of Autologous Cell Therapies and Studies of HIV Persistence

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $211,875

## Abstract

PROJECT SUMMARY/ABSTRACT
Although modern therapies have dramatically improved the outlooks for people living with HIV they are unable
to cure infection, leaving these individuals burdened by a lifelong commitment to antiretroviral (ARV) medication.
For any given individual, maintaining lifelong adherence to medication can present substantial challenges.
Moreover, many people do not have access to these expensive medications - in particular those living in
resource-limited settings. Furthermore, efforts to end the HIV epidemic have suffered from the lack of effective
preventative or therapeutic vaccines – biomedical tools which have played critical roles in the elimination of other
epidemics, such as smallpox. Recent years have seen important advances in harnessing the antibody arm of
the immune system towards these aims, though substantial challenges still exist. The T-cell arm of the immune
system, which specializes in the recognition and elimination of virus infected cells, holds great promise to
contribute to these efforts, but has lagged behind in development. This can be attributed – in part – to substantial
limitations in the suitability of currently available pre-clinical animal models for the study of T-cell responses. For
example, the property of major histocompatibility (MHC) restriction means that the ways in which the virus-
infected cells of a rhesus macaque will recognize a virus-infected cell differ from the way they would be
recognized by a given human. The current proposal aims to build upon compelling preliminary results, in which
we have observed that a relatively simple, but powerful, modification of a humanized mouse model solves many
of the key issues that have limited utility to date. Namely, we present a mouse model that can be stably engrafted
with immune cells from HIV-infected or uninfected adults, without inducing graft versus host disease (GvHD).
The use of adult cells both avoids the need for fetal tissue, and allows for the in vivo testing of the antiviral
activities of immune effectors - such as including CD8+ T-cells and natural killer cells - generated from these
human donors, in an autologous manner. These effectors could either: i) be taken directly ex vivo – to study
differences between individuals who control virus naturally vs those who do not ii) taken ex vivo following
vaccination of the human volunteer iii) or enhanced in vitro – as would model cell-therapy based approaches.
We propose experiments that we expect will the utility of the model both for testing strategies to control viral
replication, and for studying therapies which take aim at reducing or elimination the viral reservoirs that persist
through ARV therapy – towards the goal of curing infection.

## Key facts

- **NIH application ID:** 10242093
- **Project number:** 5R21AI152828-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** R. Brad Jones
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2020-08-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242093

## Citation

> US National Institutes of Health, RePORTER application 10242093, Characterization of a Memory CD4+ T-cell Humanized Mouse Model for the Evaluation of Autologous Cell Therapies and Studies of HIV Persistence (5R21AI152828-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242093. Licensed CC0.

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