# Anti-CD38 targeted alpha emitter radioimmunotherapy to eliminate multiple myeloma

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $356,167

## Abstract

PROJECT SUMMARY/ABSTRACT
The majority of patients with multiple myeloma (MM) ultimately die of progressive disease despite high rates of
initial response to novel agents. While complete response (CR) is achievable in a significant subset of patients,
most of these individuals relapse as a consequence of minimal residual disease (MRD) defined by occult foci
of treatment insensitive tumor cells clones. High dose chemotherapy followed by autologous stem cell
transplantation (ASCT) improves response, but relapse remains virtually inevitable. No modification to high
dose melphalan chemotherapy conditioning regimens has further augmented the impact of ASCT on outcome
over the past two decades. Unmodified CD38 monoclonal antibodies (MAbs) have demonstrated anti-MM
tumor cell responses and CD38 antigen targeting with β-emitter radioimmunotherapy (RIT) can eliminate
disease in pre-clinical MM models. In clinical settings however, β-emitter RIT has been associated with dose
limiting toxicity that can prevent dose escalation to levels necessary for elimination of MRD in a substantial
proportion of patients. Based on the physical characteristics of α-emitting radionuclides and new opportunities
to harness their potential, there is a compelling rationale for employing α-emitter RIT to treat MM. The α-emitter
211At deposits a very large amount of energy (~100 keV/μm) within a few cell diameters (50-90 μm) resulting in
irreparable double strand DNA breaks that overwhelm cellular repair mechanisms. We anticipate that this
combination of high energy and short path length will confer a unique capacity to kill individual targeted MM
cells and eliminate MRD with minimal radiation damage to surrounding tissues. This proposal will use 211At to
functionalize an anti-CD38 monoclonal antibody ([211At]OKT10-B10) as part of a novel approach to ASCT
conditioning. The goal of this project is to address three hypotheses: 1). [211At]OKT10-B10 will eliminate MRD
by selectively targeting all malignant plasma cells irrespective of mutational status, 2). [211At]OKT10-B10 will
disrupt the disease permissive milieu found in the bone marrow microenvironment of MM patients and 3)
[211At]OKT10-B10 will demonstrate a therapeutic index sufficient to safely sterilize all occult sites of disease.
First, we will generate clinical grade [211At]OKT10-B10 necessary to perform patient studies. Second, we will
conduct a clinical trial to a) demonstrate that [211At]OKT10-B10 localizes to MM target cells as confirmed by
direct measurement of 211At in the bone marrow and alpha camera images of target tissue; and b) evaluate the
safely of [211At]OKT10-B10 dose escalation in combination with high dose melphalan. Third, we will assess
the impact of [211At]OKT10-B10 on a) stringent complete response rates, b) MRD detected by high throughput
next generation sequencing and multi-parameter high sensitivity flow cytometry, c) the bone marrow
microenvironment, d) MM cell repopulating potential in a SCID-hu ...

## Key facts

- **NIH application ID:** 10601435
- **Project number:** 6R01CA205248-05
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Damian J. Green
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,167
- **Award type:** 6
- **Project period:** 2017-03-08 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10601435

## Citation

> US National Institutes of Health, RePORTER application 10601435, Anti-CD38 targeted alpha emitter radioimmunotherapy to eliminate multiple myeloma (6R01CA205248-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10601435. Licensed CC0.

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