# Alaska INBRE 4 One Health

> **NIH NIH P20** · UNIVERSITY OF ALASKA FAIRBANKS · 2020 · $290,737

## Abstract

PROJECT SUMMARY
Immunotherapy has become an effective treatment option for certain types of cancers but has
failed to generate significant clinical responses particularly in female patients with solid
malignancies. Recently, multiple studies have identified sex differences in cancer
immunotherapy efficacy, with males receiving the greater clinical benefit. Therefore, there is an
urgent need to develop new therapeutic modalities for the prevention and treatment of solid
malignancies while assessing sex differences in treatment efficacy. In support of this goal, we
have recently developed a liposome delivery system (C3-liposomes) that utilizes complement
C3 to specifically target antigen presenting cells (APCs). Our preliminary results show that C3-
liposome delivery of activating compounds and tumor antigen to APCs leads to T cell activation
and regression of tumors in murine cancer models. Our overall goal is to enhance activation and
tumor antigen presentation using targeted C3-liposome delivery and examine sex differences in
prophylactic immune response and treatment efficacy. Objective: This proposal will test the
hypotheses that targeted C3-liposome delivery of a tumor antigen, mucin-1 (MUC1) in
combination with therapeutic reprograming and activation of APCs prevents the development,
progression, and recurrence of cancer. Specific Aim 1: Examine sex differences in C3-
liposome prophylactic and therapeutic efficacy using a MUC1 transgenic mouse model. Study
Design: Using the C3-liposome targeted delivery system, we will deliver the tumor associated
antigen, MUC1, with therapeutics that reprogram and activate APCs in healthy and tumor
bearing transgenic MUC1 mouse models of cancer. To improve immunogenicity, we will
evaluate whether mice treated with MUC1 C3-liposomes develop a humoral antibody response
and effector and memory T cell response against MUC1. To determine C3-liposome cancer
vaccine efficacy, we will test whether MUC1 C3-liposome vaccination prevents the formation of
tumors when used prophylactically and eliminates tumors when treated therapeutically in
combination with checkpoint inhibitors. Sex differences in prophylactic immune response and
C3-liposome treatment efficacy will be examined. Impact: It’s anticipated that our findings from
this study will advance our knowledge of the immunotherapeutic approach of targeted drug and
antigen delivery to APCs. This study also has the potential to elucidate sex difference in
immune response and therapeutic efficacy of a novel nanoparticle vaccine and immunotherapy.

## Key facts

- **NIH application ID:** 10155049
- **Project number:** 3P20GM103395-20S2
- **Recipient organization:** UNIVERSITY OF ALASKA FAIRBANKS
- **Principal Investigator:** BRIAN M BARNES
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,737
- **Award type:** 3
- **Project period:** 2001-09-24 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155049

## Citation

> US National Institutes of Health, RePORTER application 10155049, Alaska INBRE 4 One Health (3P20GM103395-20S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155049. Licensed CC0.

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