# BMT CTN Core - Dana-Farber Cancer Institute and MGH Consortium

> **NIH NIH UG1** · DANA-FARBER CANCER INST · 2024 · $267,000

## Abstract

Project Summary
The promise of marrow transplantation (HCT) has been hampered by the threat of relapse, opportunistic infection
(OI) and graft-versus host disease (GVHD). These three complications interlock in a Gordian knot that have
traditionally precluded independent resolution strategies. In theory, better targeted GVHD prevention would
reduce the need for additional immunosuppression (IS) post-HCT, and subsequently lower the rates of OI, as
well as of relapse, by conserving the graft-versus tumor (GVT) effect. Transformative advances in the realm of
GVHD prevention have been possible due to creative immunomodulatory approaches targeting T-lymphocytes,
such as early in-vivo T-cell modulation (post-transplant cyclophosphamide or PTCy based strategies) and co-
stimulation blockade of the T-cell and antigen-presenting cell (APC) interaction (Abatacept/Aba). In addition, with
a deeper understanding of the role of humoral immunity in chronic GVHD (cGVHD), we and others have shown
that B-cell blockade using monoclonal antibodies can be very effective in the prevention and treatment of
cGVHD. Hence, we are entering an era in transplantation where we have in a sense, an embarrassment of riches
of potential therapeutics, but have yet to establish which of these could be the most effective GVHD prevention
strategy, to cut the proverbial Gordian knot, and result in the best patient outcomes. In this project, we focus on
the most effective strategy to prevent acute and cGVHD, while maintaining the GVT effect, with acceptable rates
of OI. First, we expand on our prior work which has shown that co-stimulation blockade of the CD28/CTLA-4
interaction with Aba (CTLA-4 Ig) results in T-cell inhibition and reduction in aGVHD lethality, first shown in murine
and non-human primate models, and then established in early phase and randomized clinical trials. We propose
to incorporate Aba with standard of care (SOC) tacrolimus (Tac) and methotrexate (MTX) peri-transplant for
reduction of aGVHD. Further, recognizing that does not prevent cGVHD, we seek to develop a cGVHD
prevention strategy adjunctive to Aba, leveraging our insights from basic murine and human studies indicating
that germinal center formation, the development of autologous and allogeneic antibodies, and B cell cytokines
are all important in the generation of cGVHD, This will further expand on our work over the last decade, showing
that CD20 targeted monoclonal antibodies (rituximab, Obinutuzumab/Obin) can effectively prevent
moderate/severe cGVHD, when given in the first year post-HCT. We propose a 2 arm, phase II randomized trial
comparing the combination of Aba/Tac/MTX/Obin (ATOM) with PTCy/Tac/mycophenolate in the myeloablative
(MAC) unrelated donor setting (URD) using peripheral blood stem cells (PBSC), to establish the most effective
transplant platform to optimize GVHD and non-GVHD outcomes. The intermediate goal is to compare the ability
of each therapy to achieve the best GVHD free relapse fre...

## Key facts

- **NIH application ID:** 10937477
- **Project number:** 2UG1HL069249-24
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** JOSEPH H ANTIN
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $267,000
- **Award type:** 2
- **Project period:** 2001-09-30 → 2031-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937477

## Citation

> US National Institutes of Health, RePORTER application 10937477, BMT CTN Core - Dana-Farber Cancer Institute and MGH Consortium (2UG1HL069249-24). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10937477. Licensed CC0.

---

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