# (Attack)2: Genetic engineering of cellular and humoral immunity to cure HIV

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $2,872,207

## Abstract

Overall: Project Summary/Abstract
The hypothesis to be tested in our U19 Program Project is that combining therapies of gene-engineered cellular
(chimeric antigen receptor (CAR)) and humoral (broadly neutralizing antibodies (bNAb)) immune reagents will
lead to a cure of HIV-1 disease. In the single remarkable case of the “Berlin patient”, allogeneic transplant of
CCR5Δ32 donor cells resulted in a functional cure without evidence for remaining HIV-1. However, a universal
unresolved limitation of transplant of gene-engineered hematopoietic stem/progenitor cells (HSPC) has been the
difficulty of achieving engraftment levels sufficient to provide good therapeutic efficacy. We propose here to focus
on building gene-engineered cellular and humoral immune therapeutics. One approach is a CAR recognizing
HIV-1 infected cells. T cell immunotherapy with tumor specific CARs delivered by adoptive T cell therapy has
proven to be effective against cancer in early human studies. We hypothesize that HSPC based delivery of CAR-
T cells can enhance the number and functional responses of the resultant engineered T cells. To complement
the engineering of T cell-mediated immunity, we also propose to engineer B cells to express bNAbs modified as
single chain variants (scFv-Fc bNAb). BNAbs directed to HIV-1 have shown promise at suppressing viremia in
animal models and clearing SHIV from the blood and tissues of infant rhesus macaques and human clinical
studies show effective suppression. Nonetheless, bNAbs require multiple injections to maintain levels required
to suppress virus in plasma and have not cleared virus in chronic infection. We will use novel lentiviral vectors
gene-engineered to target delivery of scFv-Fc bNAb into B cells in vivo without ex vivo manipulation. We
hypothesize that this strategy will promote bNAb production, biodistribution and activation/differentiation of gene-
modified B cells to clear HIV-1 reservoirs. Finally, success of these gene-modifying therapeutics depends upon
achieving sufficient systemic levels of gene-modified cells. Thus, another project will specifically address means
to modulate up or down the levels of gene-modified cells to achieve maximum therapeutic efficacy. In addition,
should any adverse effects be observed, the same reagent can be used to quickly eliminate gene-modified cells,
providing a “kill-switch”, and thus an added safety element to the overall approach.
Drs. Kitchen and Chen (UCLA) will serve as dual-PIs. Both have extensive experience in general stem cell
biology and its applications to HIV-1 disease. The Project/Core Leaders have expertise in HIV-1 biology and
gene therapeutic approaches to HIV-1 disease. The breadth of expertise ranges from vector and transgene
development (Chen, An, Morizono, Kitchen, Symonds), development and use of animal models for HSPC biology
(Kitchen, An, Morizono, Chen, Kiem), anti-HIV-1 immune function (Yang, Kitchen), understanding of HSPC
behavior (Chen) to clinical trial implem...

## Key facts

- **NIH application ID:** 9890819
- **Project number:** 1U19AI149504-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** IRVIN S.Y. CHEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,872,207
- **Award type:** 1
- **Project period:** 2020-05-07 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890819

## Citation

> US National Institutes of Health, RePORTER application 9890819, (Attack)2: Genetic engineering of cellular and humoral immunity to cure HIV (1U19AI149504-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890819. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*