# Preventing Relapse After Non-myeloablative Stem Cell Transplantation: The Final Challenge

> **NIH NIH P01** · FRED HUTCHINSON CANCER CENTER · 2021 · $1,449,399

## Abstract

PROJECT SUMMARY / ABSTRACT - OVERALL
The overall goal of this program project grant is to overcome disease relapse, which is the single-most important
limitation of allogeneic hematopoietic cell transplant (HCT) in the treatment of older or medically infirm patients
with myeloid malignancies and myeloma. Two principal approaches are proposed, understanding and enhancing
graft-vs-tumor (GVT) effects after HCT and reducing the pre-HCT tumor burden by intensifying the conditioning
regimen through innovative, first-in-human radioimmunotherapy (RIT) that has been entirely developed in our
laboratories. Project 1 will lead to an understanding of how to enhance GVT effects using studies in a in vivo
murine model and in a human in vitro model. Enhancing GVT effects will likely become an effective means of
reducing the relapse problem. Projects 2 and 3 will employ novel first-in-human RIT technology using alpha-
emitter astatine-211 (211At) conjugated to monoclonal antibodies that was first developed in murine and large
animal models. This is now applied clinically in Phase I/II trials in patients with myeloid malignancies who have
pre-HCT tumor including refractory disease and in patients with multiple myeloma. The principle addressed here
is reducing the pre-transplant tumor burden, thereby shifting the balance in favor of the transplanted allogeneic
donor lymphocytes. While RIT with an antibody to CD45, as proposed in Project 1, has been tolerated well in
the ongoing dose-escalation trial, we expect that liver toxicity will be dose-limiting for myeloid malignancies. In
order to get around that problem and to further minimize the toxicity profile of targeted RIT directed against
CD45, Project 1 proposes to develop fully anti-human CD45 MAbs, with a series of MAb isotypes/variants, and
then test the hypothesis that in vivo off-target toxicity of the RIT can be further minimized and 211At-anti-CD45
RIT be optimized by engineering of the MAb Fc portion to remove the potential to interact with Fc receptors,
especially in the liver. Clinical trials in Project 3 will begin with a CD38 target for RIT and will next optimize the
approach by switching to a B-cell maturation antigen (BCMA) target in order to achieve better efficacy of
myeloma cell kill.
In summary, work on the three projects will use a two-pronged approach at decreasing post-HCT relapse rates
among patients with myeloid malignancies and multiple myeloma, reducing the pre-HCT tumor burden and
enhancing post-HCT tumor kill through GVT effects. The outcomes of these studies have obvious bearings on
allogeneic HCT in older patients with other hematologic malignancies.

## Key facts

- **NIH application ID:** 10601299
- **Project number:** 6P01CA078902-24
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** BRENDA MARIE SANDMAIER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,449,399
- **Award type:** 6
- **Project period:** 1999-04-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601299

## Citation

> US National Institutes of Health, RePORTER application 10601299, Preventing Relapse After Non-myeloablative Stem Cell Transplantation: The Final Challenge (6P01CA078902-24). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10601299. Licensed CC0.

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