# Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $369,383

## Abstract

Project Summary
Recently, we discovered that adoptive transfer of CD39KO tumor-specific (mixed CD4+ and CD8+) T cells,
resulted in long-term survival of mice bearing large established tumors. Unexpectedly, we found that these T
cells promoted killing of antigen-loss-variants (ALVs) in vivo and prevented tumor recurrence. Moreover,
transfer of CD39KO, but not control KO, tumor-specific T cells eradicated large chimeric tumors that contained
10% of ALVs and resulted in long-term tumor-free survival and protection against rechallenge with ALV tumor
cells. Based on these novel findings, we hypothesize that transfer of tumor-specific CD39KO T cells will
eradicate large established tumors and prevent recurrence of ALV tumors, due to their ability to directly kill the
tumor cells and induce anti-ALV responses. Aim 1 will determine the contribution of type I IFN production at
the tumor site in preventing recurrence of ALV tumors. Aim 2 will determine the role of CD39KO T cells in the
recruitment of inflammatory myeloid cells and the induction of type I IFN production for tumor clearance. Aim 3
will determine whether human tumor-specific CD39KO T cells are also endowed with these abilities to
effectively eradicate human tumors in humanized mice. These innovative and mechanistic studies will shed
light on the mechanisms underlying CD39KO T cell-mediated antitumor immunity and will thus establish a
foundation for translating this discovery into more effective immunotherapies using tumor-specific T-cell
subsets in human cancers.

## Key facts

- **NIH application ID:** 10913964
- **Project number:** 5R01CA248111-05
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Yong Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $369,383
- **Award type:** 5
- **Project period:** 2021-01-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913964

## Citation

> US National Institutes of Health, RePORTER application 10913964, Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy (5R01CA248111-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10913964. Licensed CC0.

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