# Autologous chimeric antigen receptor engineered T cell immunotherapy for desensitization in patients awaiting kidney transplantation

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $3,825,129

## Abstract

Abstract
Kidney transplant is the treatment of choice for patients with end-stage renal disease (ESRD), as
it extends survival, improves quality of life and is highly cost-effective. However, for about a third
of patients on the waitlist, pre-existing anti-HLA antibodies (i.e. allo-sensitization) presents a major
barrier to successful transplant. HLA antibody responses are maintained by memory B cells
(Bmem) and plasma cells (PC). Unfortunately, desensitization approaches have been largely
ineffective due to incomplete depletion of allo-specific B cells and PCs. WE HYPOTHESIZE that
stringent depletion of donor-specific B cells and PCs is required for a clinically significant reduction
of allo-antibodies necessary to achieve successful kidney transplantation. We have shown that
engineered T cell immunotherapies employing synthetic chimeric antigen receptors (CARs) can
induce durable remission of B cell lineage and plasma cell malignancies. Two CAR-T cell
therapies that target CD19 (CART-19) and B cell maturation antigen (CART-BCMA) result in
depletion of malignant cells but also physiologic B cells and PCs. Importantly, we have shown
that CART-BCMA and CART-19 can be safely administered together. Based on this experience,
our GOAL is to leverage this innovative platform to target Bmem and PCs and promote reduction
of preformed anti-HLA antibodies, thus providing a window of opportunity for transplantation.
Specifically, we propose a single-arm proof-of-concept CLINICAL TRIAL that combines CART-19
with CART-BCMA as a novel desensitization measure in kidney transplant candidates with a
cPRA ≥99.9%. MECHANISTIC studies will evaluate the cellular, humoral and molecular immune
correlates of CART-19 + CART-BCMA immunotherapy in highly sensitized kidney transplant
candidates. These are focused on the CAR T cells, T- and B-cell immunity (both allo-specific and
protective) and, in the event of successful transplantation, the allograft biology. An INFECTIOUS
DISEASE STUDY proposal will evaluate vaccine response and immune function in our renal
transplant candidates, including our study cohort. The multi-center team (Penn, NYU, MGH)
brings together investigators with extensive experience in CART therapy, desensitization, and
outstanding depth of laboratory expertise to carry out robust mechanistic studies.

## Key facts

- **NIH application ID:** 10870041
- **Project number:** 5U01AI163087-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Vijay Bhoj
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,825,129
- **Award type:** 5
- **Project period:** 2021-08-20 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870041

## Citation

> US National Institutes of Health, RePORTER application 10870041, Autologous chimeric antigen receptor engineered T cell immunotherapy for desensitization in patients awaiting kidney transplantation (5U01AI163087-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870041. Licensed CC0.

---

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