# Immune Modulation After Allogeneic HCT

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2020 · $2,740,234

## Abstract

Program Summary
Although allogeneic hematopoietic cell transplantation (HCT) provides curative therapy for many patients with
hematologic malignancies, disease relapse and chronic graft versus-host-disease (GVHD) continue to be major
impediments to success. Both of these obstacles represent failures of immune regulation. Inadequate recognition
and destruction of residual tumor cells by a newly engrafted donor immune system permit recurrence of a
patient’s malignancy, while uncontrolled reactions against host antigens lead to GVHD. Enhancing immune
responses directed against residual leukemia cells while controlling responses directed against normal host
tissues is critical to improving patient outcomes after allo-HCT. The overall goal of this Program is to gain deeper
insight into donor and host factors that contribute to these failures and to design and implement innovative
immunologic approaches to correct them. This goal will be accomplished through clinical and laboratory studies
carried out in 3 Projects and supported by 3 Shared Resources. The projects and cores are highly interactive
and led by investigators who have collaborated in a series of studies leading to the development of provocative
clinical trials to evaluate new strategies for preventing relapse in high risk transplant recipients, treating relapse
in patients post-transplant, and tackling refractory chronic GVHD. Prevention trials include include checkpoint
inhibition with ipilumumab, engineered whole cell vaccination, and development of personalized
neoantigen/minor histocompatibility antigen vaccines. Treatment trials include combinatorial strategies pairing
checkpoint inhibitors with engineered cellular therapy to treat patients who have relapsed post-HCT. Trials in
chronic GVHD will test development of synergies between Treg expansion and B cell modulation. Dissection of
the evolution of both leukemia cells and surrounding immune cells will inform our understanding of tumor evasion
mechanisms and how they might be overcome. To this end, the Program sets out to define predictors and
mechanisms of response or resistance of AML/MDS, to determine the changes in the composition and functional
state of marrow-infiltrating immune cells, and to track evolving antigen-T cell interactions in association with
response to post-transplant immunomodulation. Additionally, further understanding how donor derived clonal
hematopoiesis shapes hematopoietic and immunologic reconstitution to influence clinical outcomes will create
new interactions that may be amenable to future interventions leading to the development of novel therapeutic
strategies. Taken together these efforts will give critical insights into understanding mechanisms of immune
dysregulation and how they lead to relapse and chronic GVHD post-HCT as well as creating novel interventions
address these obstacles to cure.

## Key facts

- **NIH application ID:** 9995438
- **Project number:** 5P01CA229092-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Robert Jon Soiffer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,740,234
- **Award type:** 5
- **Project period:** 2019-08-14 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995438

## Citation

> US National Institutes of Health, RePORTER application 9995438, Immune Modulation After Allogeneic HCT (5P01CA229092-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9995438. Licensed CC0.

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