# Novel Use of Malignant Pleural Effusion Resident T cells for Systemic Adoptive Cell Transfer in Veterans with Lung Cancer

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Systemic immune checkpoint blockade and adoptive cell transfer (ACT) therapies have been used successfully
in high mutational burden tumors such as non-small cell lung cancer (NSCLC) and melanoma, resulting in
objective response and longer survival. For ACT, surgery is often required to obtain solid tumor infiltrating
lymphocytes (TIL), which must then be isolated and expanded due to their small quantities. Alternatively,
malignant pleural effusions (MPEs) that occur in advanced NSCLC have abundant tumor and immune cells.
These are palliated with drainage, and the fluid is discarded as medical waste. However, our preliminary
observations indicate that MPEs may contain a subset of immune cells which can be activated toward anti-
tumor activity. These abundant immune cells could be a source for adoptive cell transfer therapy with the
advantages of (1) being readily available without surgery and (2) possibly requiring less expansion. I
hypothesize that there is a subset of T cells in NSCLC MPEs which can be used for ACT therapy. The
objective of this proposal is to optimize and expand tumor specific T cells from NSCLC MPEs for ACT therapy.
This proposal will undertake studies that establish critical pre-clinical data en-route to a clinical trial with
adoptive T cell transfer in Veterans with lung cancer. Thirty pleural effusions and 10 solid lung cancer tumors
will be collected as medical waste from patients undergoing clinically indicated drainage or surgery. The first
Aim will compare anti-tumor reactivity of MPE resident T cells (MPET) to traditional TIL and determine T cell
receptor repertoire and tumor mutational burden for neoepitope prediction.
The second Aim will characterize the bioenergetic state of MPET that are trapped in the metabolically hostile
environment of a pleural effusion. We will define the mechanisms of T cell metabolic dysfunction in a pleural
effusion, and also study alterations on anti-tumor activity after metabolically reprograming T cells with a
commercially available modulator of the glycolysis pathway.
The third and final Aim will determine if MPET can be successfully expanded to sufficient quantities for ACT
therapy without reaching terminal exhaustion. We will also optimize the metabolic state of MPET to enhance
activity after expansion.
Together, the proposed studies will provide insight about an unexplored tumor environment with potential to
provide large quantities of readily accessible tumor specific immune cells. This project may lead to the use of
immune cells from MPE as a source for adoptive cell transfer therapy in Veterans with NSCLC.

## Key facts

- **NIH application ID:** 10316150
- **Project number:** 5IK2CX001771-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Rajeev Dhupar
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316150

## Citation

> US National Institutes of Health, RePORTER application 10316150, Novel Use of Malignant Pleural Effusion Resident T cells for Systemic Adoptive Cell Transfer in Veterans with Lung Cancer (5IK2CX001771-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10316150. Licensed CC0.

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