# Use of Ly6K specific CAR T-cells to treat primary and metastatic triple negative breast cancer

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2022 · $174,666

## Abstract

Project Summary/abstract
 We have identified that increased Ly6K expression is associated with poor outcome in triple negative
breast cancer (TNBC). Mechanistically, Ly6K is required for the activation of TGFβ signaling and is increased in
tumorigenesis in vivo. We propose that the biomarker Ly6K is an ideal therapeutic target for the treatment of
TNBC because this protein is not expressed in normal cells, except in testis. Ly6K is also not required for vital
organ function, except for spermatogenesis. Thus, targeting this protein for the treatment of TNBC, a disease
affecting mostly females, is appropriate and ideal. Because of this, Ly6K is an optimal therapeutic target for
TNBC immunotherapy using CAR T-cells. CAR T-cells are genetically modified T cells which express a chimeric
antigen receptor fusion protein (CAR) derived from a monoclonal antibody (mAb) recognizing a target protein on
the surface of cancer cells. CAR T-cells can recognize and kill target cells expressing the target protein without
the need for HLA matching. We have generated three high affinity mAbs against human Ly6K, which recognize
the cell surface Ly6K on cancer cells. The sequences from Ly6K mAbs were used to generate a CAR in a third
generation lentiviral CAR vector to generate Ly6K-specific CAR T-cells. We will test whether Ly6K-specific CAR
T-cells will recognize cancer cells expressing cell surface Ly6K and eliminate them in primary and metastatic
TNBC mouse models.

## Key facts

- **NIH application ID:** 10477934
- **Project number:** 5R21CA256424-02
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** Geeta Upadhyay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $174,666
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477934

## Citation

> US National Institutes of Health, RePORTER application 10477934, Use of Ly6K specific CAR T-cells to treat primary and metastatic triple negative breast cancer (5R21CA256424-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10477934. Licensed CC0.

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