# BELIEVE: Bench to Bed Enhanced Lymphocyte Infusions to Engineer Viral Eradication

> **NIH NIH UM1** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $5,680,664

## Abstract

Project Abstract
This new grant application is in response to the “Martin Delaney Collaboratories for HIV Cure Research (UM1)”
RFA. We call our application “BELIEVE”, short for “Bench to Bed Enhanced Lymphocyte Infusions to
Engineer Viral Eradication”. One individual, known as the “Berlin patient”, is considered to be cured of HIV,
with no evidence for active replication competent virus in the absence of antiretroviral (ARV) therapy. The
“Mississippi” baby initially appeared to be another cure, but virus re-emerged a couple of years after ARV
cessation. ARV therapy prolongs life, but a life expectancy gap shows patients on viral suppressive therapies
live a shorter life, and have more co-morbidities. To help end the epidemic, an HIV cure is needed.
Current “shock and kill” strategies are limited in harnessing the power of immunity in seeking and removing
latent cells. Augmentation of immunity could be performed through vaccination, although therapeutic
vaccination in HIV infection has had limited efficacy to date. In addition, immune effectors in HIV infected
persons are not fully recovered with ARV treatment. There are at least three mechanisms which lead to the
inability of the immune system to remove virus completely: (1) a weakened and exhausted cytotoxic T-
lymphocyte (CTL) response from which epitope escape has occurred, (2) over activated but under performing
Natural Killer cells, and (3) inability of effector cells to reach the right sites where latent virus reside.
Our proposal has objectives, broadly defined, that are aimed at understanding how to enhance the killing ability
of HIV specific cytotoxic T lymphocytes, to augment NK cell functions, and to harness T-cell, NK cell and
antibody mediated effectors in the context of adult and pediatric HIV infections. First, we will immediately
initiate a pilot clinical study with our most promising combination of T-cell infusion and latency-reversing
agents. We will compare this combination to enhanced natural and engineered T-cells to eradicate HIV
reservoirs (in vitro, in mice, in non-human primates, and in additional human clinical studies), in association
with novel HIV Nef small molecule inhibitors. Second, we will develop and test enhanced Natural Killer cells
with or without broadly neutralizing antibodies (in mice, in non human primates, and in humans). Third, we will
target sites of viral latency which CTL cannot reach, by targeting CTL to home to reservoir sites.
We have gathered a group of accomplished investigators, with strong collaborative histories, along with
community advisors. Around 40% of the scientific leadership positions are women, and there are
representatives of early stage and minority investigators, and two corporate partners, all driven by the belief
that a cure will depend on enhancing anti-HIV immunity in association with latency reversal.

## Key facts

- **NIH application ID:** 9976444
- **Project number:** 5UM1AI126617-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** R. Brad Jones
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,680,664
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976444

## Citation

> US National Institutes of Health, RePORTER application 9976444, BELIEVE: Bench to Bed Enhanced Lymphocyte Infusions to Engineer Viral Eradication (5UM1AI126617-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9976444. Licensed CC0.

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