# Blocking lung cancer progression with peptide delivering cell therapy platforms

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

For this project we propose to assess the utility of cell therapies for delivering the anti-cancer
cytokines and chemokines in the context of non-small cell lung cancer models. Lung cancer is
the leading cause of cancer related death in the Veteran population and metastasis is a major
contributing factor to recurrence and mortality associated with non-small cell lung cancer. Aim 1
will take advantage TRAIL, a cytokine which induces apoptosis in cancer cells that is currently
being evaluated as a therapeutic modality for treating lung cancer in ongoing clinical trials. For
this project, antigen specific T cells transposon engineered to express high levels of soluble
leucine zipper modified TRAIL will be adoptively transferred using a protocol that facilitates
stable long term engraftment. The toxicity and off target effects of TRAIL cell therapy will first be
assessed in healthy mice. We will then take advantage syngeneic orthotopic models of non-
small cell lung cancer to evaluate the ability of TRAIL cell therapy to block metastasis.
Combination cell therapy with acetylsalicylic acid will be assessed as a method of enhancing
cancer cell sensitivity to TRAIL induced apoptosis and other candidate molecules that could be
used in TRAIL combination therapy will be evaluated using a GFP based apoptosis screen. Aim
2 will evaluate the hypothesis that a cell therapy delivering the chemokine CCL5 in combination
with TRAIL directly to tumors will augment immune-mediated tumor rejection. In Aim 3 we will
determine if CCL5-TRAIL combination therapy blocks cancer progression and enhances
survival in a murine orthotopic NSCLC model. This project represents a unique opportunity to
examine the utility of delivering anticancer peptides with a cell therapy platform in the context of
an immune competent mouse model of NSCLC. These studies will be useful in determining the
efficacy of chronic systemic TRAIL therapy and tumor targeted CCL5/TRAIL combination
therapy for blocking progression of lung cancer and augmenting tumor rejection.

## Key facts

- **NIH application ID:** 9926708
- **Project number:** 5IK2BX004585-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Richard Thomas O'Neil
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926708

## Citation

> US National Institutes of Health, RePORTER application 9926708, Blocking lung cancer progression with peptide delivering cell therapy platforms (5IK2BX004585-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9926708. Licensed CC0.

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