# Regulatory Dendritic Cell Therapy in Live Donor Renal Transplant Recipients

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $716,939

## Abstract

Project Summary/Abstract
Based on pre-clinical studies, a compelling rationale has emerged for clinical testing of regulatory dendritic
cells (DCreg) to improve organ transplant survival. Importantly, using a robust, clinically-relevant, non-human
primate model and minimal immunosuppression, we have shown that infusion of DCreg, one week before
transplant, can safely prolong renal allograft survival, without evidence of host sensitization. This therapeutic
effect is associated with selective attenuation of donor-specific T memory cell responses, an important barrier
to promotion of long-term graft survival. We have generated GMP grade human DCreg from elutriated blood
monocytes and demonstrated both their stable resistance to maturation under inflammatory conditions in vitro
and their ability to negatively regulate alloreactive T cell responses. We have also established release criteria
for clinical testing. Based on these accomplishments and with the support of an R34 clinical trial planning
grant, we have, in conjunction with DAIT program officers, completed the clinical trial protocol. We have also
finalized scale-up manufacturing SOPs for DCreg production, completed design of the mechanistic studies,
obtained the requisite approval (IND) from the FDA, established the framework for clinical trial operation and
management, and the statistical considerations and analytical plan. We are thus well-prepared and ready to
conduct the proposed clinical trial. This is a novel and unique approach to regulatory immune cell therapy in
organ transplantation.
We hypothesize that donor-derived DCreg, generated ex vivo and administered prospectively to live donor
renal transplant recipients treated with conventional immunosuppression, will be safe and induce
immunological changes conducive to improved graft survival. Our two Specific Aims are: Aim 1: To conduct a
first-in-human, open-label, single center phase 1 dose escalation safety study in adult recipients of de novo,
live donor renal transplants. Patients will receive standard-of-care immunosuppression. One week before
transplantation, however, they will receive a single infusion of donor-derived DCreg in combination with
mycophenolic acid. While this is a safety and feasibility trial, data that we acquire during the course of the trial
may enable us to conduct a preliminary examination of efficacy. Aim 2: To conduct sequential immunological
analyses of the DCreg recipients. We will perform detailed mechanistic studies critical to understanding the
outcome of the study and potential effects of the infused cells on the alloimmune response.

## Key facts

- **NIH application ID:** 10153679
- **Project number:** 5U01AI136779-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Angus W Thomson
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $716,939
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153679

## Citation

> US National Institutes of Health, RePORTER application 10153679, Regulatory Dendritic Cell Therapy in Live Donor Renal Transplant Recipients (5U01AI136779-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153679. Licensed CC0.

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