# Exploring CD38 molecular biology and imaging in multiple myeloma pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $637,629

## Abstract

Multiple myeloma (MM) is the 2nd most common, age related, hematological malignancy with an estimated
30,000 new cases and 13,000 deaths per year. Patients with upfront refractory disease progress fast, and those
that enter remission eventually die as a consequence of relapsed disease. To increase patient survival, clinicians
need new ways of selecting effective and durable therapies for relapsed and refractory MM patients. Antibody
(Ab) based treatments that target cluster of differentiation 38 (CD38), a transmembrane protein consistently
expressed in MM cells, is a promising therapy for relapsed and refractory MM patients. Currently, there are three
CD38 targeted monoclonal Abs (mAbs) in the clinic for MM patients, daratumumab, isatuximab and MOR-202.
These Abs are safe, well tolerated and show remarkable efficacy in ~30% of myeloma patients. It is unknown
why the majority of remaining patients do not respond to CD38 targeted mAb therapy and why there is such
variability between patients. Functionally, CD38 is a pleiotropic antigen that acts as an enzyme as well as a
receptor. The extracellular enzymatic component of CD38 is responsible for the metabolism of nicotinamide
adenine dinucleotide (NAD) to downstream Ca2+ signaling molecules. There is growing evidence that variability
in CD38 targeted therapy response in MM cells could in large part be contributed to the changes in its NAD
enzymatic activity. Here, we posit that while CD38 expression is important, the monitoring of CD38 enzymatic
activity in concert with spatiotemporal imaging is key to linking MM response to CD38 targeted therapies. We
propose to address this question using Positron Emission Tomography (PET), which is a powerful molecular
imaging tool that can be directly applied to quantify receptor expression and functional activity in vivo, non-
destructively and longitudinally. We have shown that PET imaging of CD38 antigen on MM cells is feasible using
the radiolabeled CD38 mAb daratumumab. A limitation of this approach however is that Abs are not suited for
longitudinal imaging studies due to their long biological half-life. High-affinity peptide based small molecule
imaging agents can effectively overcome these limitations since they are rapidly taken up by tumor tissue while
being promptly cleared from non-target organs in vivo. Despite the unmet need, there is a paucity of CD38
targeted small molecule peptide based PET probes for MM. Using innovative phage display technology, we will
develop new CD38 targeted peptide-based PET imaging probes that are specific for enzymatically activate CD38
conformation. Furthermore, in highly relevant biological systems, we will evaluate molecular pathways as well
as spatial relationships that govern MM-associated CD38 expression. The specific aims are: (1) Aim 1a. Identify
and validate changes in CD38 expression and enzymatic activity before and after CD38 targeted therapies in
human mouse models of MM. Aim 1b. Evaluate spatiotemporal CD3...

## Key facts

- **NIH application ID:** 10052182
- **Project number:** 1R01CA248493-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Monica Shokeen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $637,629
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052182

## Citation

> US National Institutes of Health, RePORTER application 10052182, Exploring CD38 molecular biology and imaging in multiple myeloma pathogenesis (1R01CA248493-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052182. Licensed CC0.

---

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