# Increasing Thiols for Improving T cell Immunotherapy

> **NIH NIH R41** · LIPO-IMMUNO TECH, LLC · 2022 · $394,167

## Abstract

ABSTRACT
New strategies to improve adoptive cell therapy (ACT) protocols are emerging to enhance in vivo persistence of
adoptively transferred tumor epitope-specific T cells and overcome tumor-induced immunosuppression. Our
preliminary data suggests that there is a direct correlation between the long-lived central memory T cells (Tcm)
and their anti-oxidant capacity. Overexpression of thioredoxin-1 (Trx), a critical molecule that regulates cell-
surface thiols (c-SH), increased Tcm phenotype in T cells obtained from TCR transgenic mouse crossbred with
Trx transgenic mouse, or engineering human T cells with a retroviral vector with TCR and Trx together. These
preliminary observations led us to hypothesize that “the presence of Trx drives tumor-reactive T cells to a c-SHhi
phenotype, which results in increased persistence in the oxidative tumor microenvironment and improved tumor
control." We propose to further strengthen the translational aspect of this strategy by determining if strategies to
increase anti-oxidant capacity in presence of recombinant thioredoxin (rTrx) can reprogram tumor-infiltrating
lymphocytes and improve TIL-mediated ACT. The experiments are planned under the following specific aims: 1)
To determine if human tumor-derived TILs could be ex vivo programmed with rTRx and exhibit enhanced anti-
tumor phenotype, 2) To establish if rTrx TILs are superior to conventional TILs in controlling tumor growth in
vivo. We believe that our studies are innovative and will uncover essential aspects that need to be considered
when generating tumor-specific Tcm/Tscm cells for the ACT and enhance its wider use by decreasing the
prohibitive costs.

## Key facts

- **NIH application ID:** 10603006
- **Project number:** 1R41CA271958-01A1
- **Recipient organization:** LIPO-IMMUNO TECH, LLC
- **Principal Investigator:** Shikhar Mehrotra
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,167
- **Award type:** 1
- **Project period:** 2022-09-13 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10603006

## Citation

> US National Institutes of Health, RePORTER application 10603006, Increasing Thiols for Improving T cell Immunotherapy (1R41CA271958-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10603006. Licensed CC0.

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