# Engineered T Cells Targeting Abnormal Glycans in Metastatic Prostate Cancer

> **NIH VA IK2** · PHILADELPHIA VA MEDICAL CENTER · 2020 · —

## Abstract

1. Objective(s): This proposal aims to profile abnormal glycosylation in prostate tumors of
veterans, to determine if engineered chimeric antigen receptor (CAR) T cells targeting
abnormally glycosylated proteins will demonstrate efficacy against bone-metastatic prostate
cancer, and to evaluate mechanisms to improve T cell trafficking to tumor sites and enhance
resistance to immunosuppression.
2. Research Design: De-identified veteran prostate cancers will be assembled into tumor
tissue microarrays and profiled for abnormally glycosylated proteins through
immunohistochemical and histopathological techniques, evaluated for spatial N-glycosylated
epitopes through MALDI-TOF imaging, and characterized for O-glycosylated through cellular O-
glycome reporter and amplification. An animal model of bone-metastatic prostate cancer will be
developed through engraftment of a human osteoblast scaffold to support the bone-enrichment
of implanted prostate cancer cell lines in NOD-SCID IL2R null (NSG) immunodeficient mice.
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Xenograft animals will be treated with a single intravenous dose of human CAR T cells (n=10
per treatment group) to measure the efficacy and potential treatment limitations of adoptive
immunotherapy for bone metastases. Lastly, genetic engineering approaches will be evaluated
to improve T cell bone homing and increase resistance to immunosuppression, including ectopic
chemokine receptor expression and gene-disruption of immune checkpoint molecules.
3. Findings: Preliminary results demonstrate strong expression of Tn-MUC1 in bone-
metastatic prostate cancer.
4. Clinical Relationships: CAR T cells have been explored in the clinic for over 6 years, have
demonstrated remarkable success for hematopoietic malignancies, but have lacked sufficient
clinical success in solid tumors. Nearly 10,000 veterans are diagnosed with prostate cancer per
year and bone-metastatic prostate cancer remains a significant treatment challenge. Successful
findings from this study could develop new treatment options for veterans with prostate cancer
as well as improve CAR T cell adoptive immunotherapy for solid tumors.

## Key facts

- **NIH application ID:** 9863993
- **Project number:** 5IK2BX004183-03
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Avery D. Posey
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863993

## Citation

> US National Institutes of Health, RePORTER application 9863993, Engineered T Cells Targeting Abnormal Glycans in Metastatic Prostate Cancer (5IK2BX004183-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9863993. Licensed CC0.

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