# Induction of autosis to overcome resistance in adoptive cell therapy for solid tumors

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2024 · $539,865

## Abstract

Project Summary
Adoptive cell therapy is a promising approach to treat cancer, but despite tremendous efforts, results of clinical
trials in human solid tumors using ACT with tumor-specific T cells expressing T-cell-receptors (TCR) or
chimeric antigen receptors (CAR) have not demonstrated the desired therapeutic responses. Recently, we
developed tumor-specific T cells loaded with the myxoma virus to overcome resistance in solid tumor ACT. We
hypothesize that anti-solid tumor activity of these T cells is mainly attributed to a special type of tumor cell
death, autosis, that has not been considered a T cell killing mechanism before but may contribute to the
observed exciting antitumor potency by targeting both antigen-positive and antigen-negative tumor cells. Aim 1
will determine the unique molecular mechanism underlying tumor cell autosis induced by the synergy of
myxoma virus-derived factor(s) with T cell-derived soluble factor(s). Aim 2 will determine the role of these
tumor-specific T cells in promoting autosis and robust host immunity to eradicate solid tumors when the
targeted antigen is expressed by only ~25% of tumor cells. Our proposed studies will identify a novel ACT
strategy endowed with the capacity to eliminate solid tumors with very high antigen heterogeneity. This
translationally relevant work holds promise to significantly advance the therapeutic index of ACT in solid
tumors and could then lay the foundation for future clinical trials.

## Key facts

- **NIH application ID:** 10794408
- **Project number:** 5R01CA278911-02
- **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:** $539,865
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794408

## Citation

> US National Institutes of Health, RePORTER application 10794408, Induction of autosis to overcome resistance in adoptive cell therapy for solid tumors (5R01CA278911-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10794408. Licensed CC0.

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