# PLA2G2D Antibodies for Cancer Immunotherapy

> **NIH NIH R43** · APEXIMMUNE THERAPEUTICS INC. · 2023 · $399,618

## Abstract

PROJECT SUMMARY / ABSTRACT
Currently approved immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, most
patients do not respond to these treatments because of primary or acquired resistance. Identifying new immune
regulators and developing therapeutics targeting such molecules is a current focus in immuno-oncology. We
have found that the secreted phospholipase A2 PLA2G2D is highly expressed in various human tumors and
positively correlated with that of classic checkpoints such as CTLA-4, PD-1, and PD-L1. PLA2G2D potently
diminishes dendritic cell function, suppresses T cell activity, and promotes macrophage M2 polarization.
Accordingly, studies using genetically-engineered loss- or gain-of-function mice demonstrate that PLA2G2D
strongly enhances tumor growth, indicating that PLA2G2D is a novel, targetable checkpoint for tumor
immunotherapy. We have generated more than 700 anti-PLA2G2D monoclonal antibodies, and using a series
of in vitro biochemical and immune cell functional assays we have identified 39 leading function-blocking
candidates. This proposal seeks to evaluate the anti-tumor efficacy of the 5 most functionally potent drug
candidates (which do not cross-react with mouse PLA2G2D), alone and in combination with existing ICIs, using
syngeneic tumor models in transgenic PLA2G2D-humanized mice. We will also assess how anti-PLA2G2D
changes the tumor immune profile and histologically evaluate PLA2G2D protein expression in various human
tumors using our drug candidate (Aim 1). The best drug candidate identified in Aim 1 will then be subjected to
non-GLP maximum tolerated dose toxicity and toxicokinetic evaluation in cynomolgus monkeys (Aim 2).
Collectively, the successful execution of this proposal will enable us to nominate our final lead molecule and
begin IND-enabling studies as part of a follow-up phase II SBIR proposal. Ultimately, an efficacious therapeutic
anti-PLA2G2D antibody will comprise a new treatment for patients resistant to currently available ICIs.

## Key facts

- **NIH application ID:** 10699504
- **Project number:** 1R43CA278134-01A1
- **Recipient organization:** APEXIMMUNE THERAPEUTICS INC.
- **Principal Investigator:** LI-FEN LEE
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $399,618
- **Award type:** 1
- **Project period:** 2023-06-09 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10699504

## Citation

> US National Institutes of Health, RePORTER application 10699504, PLA2G2D Antibodies for Cancer Immunotherapy (1R43CA278134-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10699504. Licensed CC0.

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