# A Phagocytosis Modulating Nanomedicine for Targeted Breast Cancer Immunotherapy

> **NIH NIH K08** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $253,377

## Abstract

Project Summary
 Despite significant advances in the treatment of breast cancer, the metastatic form of the disease remains
highly lethal, with a 5-year overall survival rate of only around 20%. Even with the use of new, targeted
therapies such as antibodies against the human epidermal receptor 2 (HER2) expressed by cancer cells, over
70% of patients with metastatic diseases eventually become resistant to therapy. Advances in cancer
immunotherapy with immune checkpoint blockers have shown that harnessing the power of the body's immune
system can be an effective strategy to fight metastatic cancer. However, only a small proportion of patients
(~20%) respond to immune checkpoint blockers, and their effectiveness against breast cancer remains
uncertain. To overcome these challenges, we recently developed a multivalent bispecific nanobioconjugate
engager (mBiNE) that simultaneously engages HER2 receptor on breast cancer cells and pro-phagocytosis
molecules on macrophages to facilitate the clearance of HER2+ breast cancer by the immune system. The
current proposal explores the use of mBiNE to promote antitumor immune responses and to enhance the
effectiveness of immune checkpoint blockade against metastatic breast cancers. Aim 1 of the proposal will
examine whether mBiNE activates potent and broad antigen-specific antitumor immune responses against
HER2 overexpressing metastatic breast cancer. For Aim 2, we will elucidate the innate mechanisms within
macrophages by which mBiNE-induced tumor cell phagocytosis promotes the cross-priming of adaptive
antitumor immune responses. Finally, for Aim 3, we will investigate whether mBiNE can be safely combined
with anti-PD1 therapy to stimulate both the innate and adaptive immune responses against poorly
immunogenic metastatic breast cancer.
 An extensive training and development program has been proposed under the guidance of a
multidisciplinary mentoring team consisting of physician-scientists, oncologists, immunologists, and tumor
biologists. My primary mentor, Dr. Yang-Xin Fu, is a physician scientist, and a recognized expert in innate
tumor immunity; my co-mentor, Dr. Wendy Woodward is known for her preclinical and clinical work with
aggressive types of breast cancers. They will be joined on my mentoring committee by Dr. Irving Weissman, a
pioneer in tumor immunology; Dr. Keith Knutson, a leader in breast cancer vaccine development; and Dr.
Patrick Hwu, an internationally recognized cancer immunotherapy expert, who will serve as an advisor. The
University of Texas Southwestern Medical Center provides an outstanding environment for my research and
career development. All of the resources and equipment critical to the proposed research are readily available
on campus, and I will have many opportunities to form collaborations with leaders in cancer immunotherapy.
Together, the proposed research, training and career development plan will ensure that I receive the best
mentorship available to become an independe...

## Key facts

- **NIH application ID:** 9965883
- **Project number:** 5K08CA241070-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Wen Jiang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $253,377
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965883

## Citation

> US National Institutes of Health, RePORTER application 9965883, A Phagocytosis Modulating Nanomedicine for Targeted Breast Cancer Immunotherapy (5K08CA241070-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965883. Licensed CC0.

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