# TLI and ATG Conditioning for Combined Kidney and Blood Stem Cell Transplantation

> **NIH NIH P01** · STANFORD UNIVERSITY · 2020 · $544,686

## Abstract

Project Summary/Abstract
The goal of the proposed clinical study is to induce tolerance to combined kidney and hematopoietic cell
transplants after conditioning with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) in patients
given grafts from related living HLA haplotype matched donors or from unrelated living donors who are
matched at 3 HLA antigens. Establishment of tolerance is expected to eliminate the usual lifelong need for
immunosuppressive (IS) drugs and attendant side effects such that complete IS drug withdrawal will be
accomplished without subsequent evidence of rejection. The proposed studies build upon our progress in the
previous grant periods in the successful induction of chimerism and tolerance in about 80% of fully HLA
matched patients, the ability to establish persistent high levels of mixed chimerism in related HLA haplotype
matched patients, and the 100% kidney graft survival in 25 HLA matched and 20 HLA mismatched patients
enrolled in the tolerance protocols during the past 15 years. We will test the hypothesis that high levels of
mixed chimerism that persist for more than 1 year will be maintained during and after IS drug withdrawal, and
result in tolerance. We hypothesize that tolerance will be predicted by evidence of alloreactive T cell clonal
deletion measured by high throughput sequencing of TCR genes, lack of development of donor specific
antibodies (DSA), and lack of inflammatory cell PCR products in the urine. The changes in the lymphoid
tissues that promote tolerance after conditioning will be monitored by determining changes in the balance of
effector T cells and immunosuppressive regulatory cells including monocytes and myeloid derived suppressor
cells (MDSCs) in the blood. In order to assess the longterm outcome of patients, we propose to establish a
registry of efficacy and risks for all patients enrolled in our tolerance protocols since inception for comparison to
standard of care patients in our centers and in the national registry. In addition, we will perform longterm
immune monitoring parameters to measure persistence of chimerism, donor specific unresponsiveness in the
MLR, and the T cell clonal repertoire. In conclusion, we will attempt to induce tolerance, identify mechanisms
and predictors such that IS drugs can be guided appropriately, and determine the durability of immune
changes that underlie tolerance.

## Key facts

- **NIH application ID:** 9931282
- **Project number:** 5P01HL075462-15
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** SAMUEL STROBER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,686
- **Award type:** 5
- **Project period:** — → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931282

## Citation

> US National Institutes of Health, RePORTER application 9931282, TLI and ATG Conditioning for Combined Kidney and Blood Stem Cell Transplantation (5P01HL075462-15). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9931282. Licensed CC0.

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