# Antigenic basis of immune responses after immune modulatory therapies post-HCT

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2021 · $576,722

## Abstract

Project Summary
Allogeneic hematopoietic stem cell transplantation (HCT) is an established immune-based therapy for acute
myelogenous leukemia (AML), and provides a setting for dissecting the immune basis of response and
resistance to immunologic selective pressure. In particular, HCT provides an effective platform for subsequent
immunomodulation to enhance graft-versus-leukemia (GvL) effects, and is thus an opportunity to develop
combinatorial therapy. At DFCI, we have advanced the engineering of combinations of HCT with other immune
modalities over two decades, including through phase I studies of post-HCT donor lymphocyte infusion (DLI),
whole tumor cell vaccines, and checkpoint blockade antibody (CPB) therapy, by which we have evaluated the
impact of the various components of these combined therapies. For example, we previously reported that
patients with chronic myeloid leukemia who generated detectable marrow-infiltrating CD8+ T cells after HCT
were more likely to develop durable remission to DLI, and that DLI response was associated with reversal of
transcriptional signatures of T cell exhaustion, consistent with the provision of `immunologic help' (Bachireddy
Blood 2014). We hypothesize that dissection of how leukemia cells and their surrounding immune cell
populations co-evolve in relationship to allo-HCT course will provide essential insights for undertaking
the rational design of effective combination therapy. We focus on studies of AML following HCT, as
several informative clinical trials have been recently completed at DFCI (Project 1). Using modern
immunogenomic tools (Core 3) and clinical factor association analysis (Core 1), we will map how leukemia and
donor immune cells co-evolve following HCT in order to better strategize about the design of future studies of
post-HCT immunomodulatory therapy. We will leverage our expertise in the study of clonal evolution to
investigate the immunogenomic features of AML cells (i.e. neoantigen and minor histocompatibility antigen
(mHAg) load, somatic mutations in antigen processing/presentation machinery) of ~200 pre-HCT leukemias
(samples provided by Core 2) in relation to subsequent outcome following HCT alone, or with post-HCT
vaccines, DLI or CPB (Core 1), and integrate genetic and transcriptional information from matched pre- and
post-transplant relapse leukemia samples to identify the basis of immunologic escape following exposure to
immune-based selective pressure (Aim 1). In parallel, we will determine the changes in the composition and
functional state of marrow-infiltrating immune cells following post-HCT immunomodulation through single cell
transcriptome characterization of samples collected from patients with defined response profiles (Aim 2).
Finally, we will track evolving antigen-T cell interactions in association with response to post-transplant
immunomodulation in which we will link the antigen specificity (i.e. predicted personal neoantigens, leukemia-
associated antigens, mHA...

## Key facts

- **NIH application ID:** 10218090
- **Project number:** 5P01CA229092-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Catherine Ju-Ying Wu
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $576,722
- **Award type:** 5
- **Project period:** 2019-08-14 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218090

## Citation

> US National Institutes of Health, RePORTER application 10218090, Antigenic basis of immune responses after immune modulatory therapies post-HCT (5P01CA229092-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218090. Licensed CC0.

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