# Novel Drug for Cancer Immunotherapy that Targets Phosphatidylserine

> **NIH NIH R43** · IMMUNE MODULATORY THERAPIES, LLC · 2021 · $293,178

## Abstract

Abstract
Phosphatidylserine (PS) is emerging as an attractive immunotherapeutic target in the light of mounting evidence
highlighting its causal link to immune suppression. We have established that exosomes derived from melanoma
and ovarian tumor microenvironments express PS on their surfaces and suppress multiple activation endpoints
of T cells triggered through the T cell receptor. Studies have also shown that expression of PS on the surface of
many non-apoptotic cancer cells lead to immunosuppression. Recent clinical studies in melanoma patients
demonstrated that exosomes that are released from patient tumors suppress T cell tumor killing and contribute
to tumor progression. We have designed and synthesized a new compound, Zn-DPA)6-DP-15K (ExoBlock) that
binds to phosphatidylserine with high avidity. ExoBlock was shown to consistently and significantly block the
immune suppressive activity of exosomes derived from melanoma and ovarian tumor microenvironments in vitro.
Based upon these findings, we predicted that ExoBlock would enhance the killing of tumor cells by T cells in
tumor xenografts due to its binding to PS on the exosomes, tumor and apoptotic cells, representing a multi-
pronged approach. We tested this prediction using two different human tumor xenograft models: a) the previously
validated in-house developed omental tumor xenograft (OTX) model established using patient-derived ovarian
tumors, and b) the recently developed and validated Xenomimetic mouse (X-mouse) model that allows us to
quantify and establish the efficacy of multiple T cell-stimulating immune-based therapies pre-clinically. This
model uses melanoma patient-derived tumor-specific T cells that are adoptively transferred into immunodeficient
mice bearing melanoma xenografts expressing tumor neo-antigens recognized by the T cells. The therapeutic
efficacy of ExoBlock was next established by significantly enhancing tumor suppression in both the OTX and X-
mouse models, and was found to be comparable to anti-PD-1 therapy in X-mouse model. Together, these results
have laid the foundation and rationale for our work proposed in the Phase I application. Additional toxicity and
pharmacokinetic (PK) studies are proposed for ExoBlock in Aim 1. The PK studies will help to determine the
optimal dose, schedule and delivery method of ExoBlock that will be tested in aim 2. In Aim 2 ExoBlock will be
tested in vivo for its therapeutic efficacy in omental tumor xenograft (OTX) model consisting of patient-derived
ovarian tumor and syngeneic mouse melanoma model with B16-F10 tumor. Our rationale for using both a human
and mouse tumor model is discussed in the Approach. The results of this Phase 1 study will lay the foundation
for a more extensive study in a future phase 2 study that will lead to an IND and clinical trial of ExoBlock.

## Key facts

- **NIH application ID:** 10254727
- **Project number:** 1R43CA257721-01A1
- **Recipient organization:** IMMUNE MODULATORY THERAPIES, LLC
- **Principal Investigator:** RICHARD B BANKERT
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $293,178
- **Award type:** 1
- **Project period:** 2021-03-11 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254727

## Citation

> US National Institutes of Health, RePORTER application 10254727, Novel Drug for Cancer Immunotherapy that Targets Phosphatidylserine (1R43CA257721-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10254727. Licensed CC0.

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