# OPN neutralization monoclonal antibody 100G2 for human pancreatic cancer immunotherapy

> **NIH NIH R43** · CHEMEDIMMUNE, INC. · 2020 · $329,610

## Abstract

Project Summary
 According to the American Cancer Society, the 5-year overall survival rate of pancreatic cancer patients is
approximately 9%. Gemcitabine is the standard therapy for pancreatic cancer, but it only increases patient
survival by about 5 weeks. Despite breakthroughs in immune checkpoint inhibitors (ICI) immunotherapy in many
types of human cancer. Pancreatic cancer stands out as one of the few human cancers that does not respond
to ICI immunotherapy. New therapies therefore are in urgent need for pancreatic cancer. The underlying
mechanism of pancreatic cancer non-response to ICI immunotherapy is currently unknown. One notion is that
pancreatic cancer is a type of “cold or nonimmunogenic” cancer that lacks cytotoxic T lymphocyte (CTL) tumor
infiltration. We have recently shown that CTL infiltrates are present in the human pancreatic carcinoma and
human pancreatic tumor cells express abundant PD-L1. Furthermore, literatures have shown that myeloid-
derived suppressor cells (MDSCs) are abundant in the pancreatic cancer, and we and others have determined
that MDSCs suppress CTLs through both PD-L1-dependent and PD-L1-independent mechanisms. It is therefore
likely that CTLs are also suppressed by a PD-L1-independent mechanism that compensates for PD-L1 function
in the pancreatic tumor microenvironment. We discovered in mouse tumor models and human cancer patients
that osteopontin (OPN) acts as another immune checkpoint that negatively regulates T cell activation. Our
published data and unpublished preliminary studies demonstrated strong scientific promise to target OPN to
suppress pancreatic cancer immune evasion. Highly relevant to this proposal, we have developed a first-in-class
OPN neutralization monoclonal antibody that is potent in reversing OPN-mediated suppression of T cell
activation. Our central hypothesis is that OPN compensates for PD-L1 function in suppression of CTL activation
and OPN mAb is effective in rendering pancreatic cancer response to ICI immunotherapy. To test this
hypothesis, we will pursue the following two specific aims: 1) test the hypothesis that neutralizing OPN function
increases the efficacy of anti-PD-1 immunotherapy in suppression of pancreatic cancer in vivo; and 2) humanize
OPN mAb for human pancreatic cancer immunotherapy. Successful completion of the proposed studies has the
potential to develop a humanized OPN monoclonal antibody for human pancreatic cancer immunotherapy.

## Key facts

- **NIH application ID:** 10009769
- **Project number:** 1R43CA250780-01
- **Recipient organization:** CHEMEDIMMUNE, INC.
- **Principal Investigator:** Priscilla Simon Redd
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $329,610
- **Award type:** 1
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10009769

## Citation

> US National Institutes of Health, RePORTER application 10009769, OPN neutralization monoclonal antibody 100G2 for human pancreatic cancer immunotherapy (1R43CA250780-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10009769. Licensed CC0.

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