# B7x in Cancer: Mechanisms and Therapies

> **NIH NIH F30** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $51,036

## Abstract

PROJECT SUMMARY
 Cancer is the second-leading cause of death in the United States, causing nearly 600,000 deaths each
year. A critical aspect of cancer progression is evasion of the immune system. The B7 and CD28 families of
ligands and receptors mediate essential costimulatory or coinhibitory pathways; pathways that promote or
suppress the immune system, respectively. B7x (B7-H4, B7S1 or VTCN1) is a newly discovered member of
the B7-family that inhibits T-cell proliferation and effector functions. It is frequently overexpressed in a wide
variety of human cancers, and is generally correlated with advanced disease status and poorer clinical
outcomes. Previously, we demonstrated in a mouse model that B7x promotes tumor metastasis and promotes
immunosuppressive cell populations such as myeloid-derived suppressor cells (MDSCs). Further, we also
showed that blockade of B7x reduces tumor metastasis, alters the tumor-infiltrating immune population to favor
anti-tumor effector cells, and confers long-term immunity against tumor rechallenge. Thus, we propose two
aims: (1) Elucidate the regulation and function of B7x and its role in tumor progression (2) Develop and
characterize anti-B7x therapy and its effect on tumor-infiltrating immune cells. For our first aim, we will explore
tumor-associated hypoxia as a mechanism for B7x expression. Further, we will characterize the effects B7x
has on the survival and generation of MDSCs. Lastly, we will investigate the role of B7x in tumor development
and progression in vivo by generating a mouse spontaneous cancer model. In our second aim, we will develop
and characterize B7x-targeted therapy. First, we have generated several clones of human B7x-specific
monoclonal antibodies, which we will test for efficacy with our experimental metastasis model in vivo. Next, in
context of the long-term anti-tumor immunity conferred by anti-B7x therapy, we will investigate how B7x
blockade alters memory T-cell populations. Lastly, we will test B7x blockade in combination with established
checkpoint inhibitors and determine if combination therapy has synergistic effects. With these studies, we seek
to gain a better understanding of the functional contribution of B7x to tumor progression, and establish it as a
prime target for immunotherapy.

## Key facts

- **NIH application ID:** 10084280
- **Project number:** 5F30CA224931-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Peter John
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2018-02-22 → 2023-02-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084280

## Citation

> US National Institutes of Health, RePORTER application 10084280, B7x in Cancer: Mechanisms and Therapies (5F30CA224931-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10084280. Licensed CC0.

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