# Nongenotoxic conditioning for HIV cure transplantation approaches

> **NIH NIH U19** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $399,503

## Abstract

Abstract
 The cure of HIV using hematopoietic stem cell (HSC) transplant is supported from the
experience of the `Berlin patient'. Recent results from patients in London and Düsseldorf are very
encouraging and potentially bolster transplant as a cure for HIV. What remains a challenge is to
reduce the complexity of hematopoietic stem cell transplant so that it may be more readily adopted
in settings that are not acutely life threatening such as chronic HIV disease. Gene editing will
make autologous cell transplant possible thereby eliminating the devastating complication of graft
versus host disease and address limited availability of allogeneic CCR5 ∆32/∆32 donors. However,
`conditioning' to enable stem cells to engraft the marrow is highly toxic and requires resource
intensive hospitalization as currently practiced.
 We aim to develop nongenotoxic conditioning (NGC) that leverages antibody drug conjugates
(ADCs) to specifically target and deplete hematopoietic cell populations as a niche sparing
method with reduced toxicity. By investigating ADCs that are HSPC-specific (anti-CD117
targeting) or more broadly immune depleting (anti-CD45 targeting), we aim to identify the optimal
NGC strategy for enabling efficient HSC transplant in immunodeficiencies. We will combine our
ADC-based conditioning with autologous gene-modified cell transplants in animal infection
models to identify a lead strategy with translational value. The specific aims of this project are:
Specific aim 1. Optimize the dose and schedule of treating NHP with anti-CD117 ADC to achieve
durable donor chimerism.
Specific aim 2. Optimize the dose and schedule of treating NHP with anti-CD45 ADC to achieve
durable donor chimerism.
Specific aim 3. Determine whether nongenotoxic conditioning and gene-modified HSC
transplant enable disease control in infected animals.
 If successful, this project will provide specific interventions that can lower the barrier for gene
modified HSC transplantation as an approach to cure HIV/AIDS.

## Key facts

- **NIH application ID:** 10409804
- **Project number:** 5U19HL156247-03
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Glen D Raffel
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $399,503
- **Award type:** 5
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409804

## Citation

> US National Institutes of Health, RePORTER application 10409804, Nongenotoxic conditioning for HIV cure transplantation approaches (5U19HL156247-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10409804. Licensed CC0.

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