# Genetically engineering T cells to overcome the immunosuppressive melanoma microenvironment

> **NIH NIH F32** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $65,958

## Abstract

ABSTRACT
While checkpoint immunotherapy has transformed the treatment of metastatic melanoma over the past
decade, this therapy fails to provide durable responses for the majority of patients. Immunotherapy resistance
in solid tumors is often driven by the immunosuppressive tumor microenvironment (TME), which dampens the
anti-tumor capacity of incoming T cells. In this proposal, I aim to genetically engineer T cells to overcome a key
pathway of immunosuppression which I identified using an unbiased bioinformatics screen. I aim to improve
the function of adoptively transferred T cells by using CRISPR to knockout the expression of this key immune
inhibitory receptor expressed on the T cell surface. I have already developed a method to knockout this gene
efficiently in murine and human T cells, and through this proposal, I will determine the effect of gene knockout
on intrinsic T cell fitness and function (Aim 1), T cell accumulation and function in the melanoma
microenvironment (Aim 2), and T cell anti-tumor efficacy (Aim 3). I expect that this research will yield a
translational method to improve the function of adoptively transferred T cells in the immunosuppressive
melanoma TME. Our team has demonstrated the ability to take novel T cell therapies from the lab to the clinic,
and our established program to treat patients with genetically-engineered T cells will ease translation.

## Key facts

- **NIH application ID:** 10066180
- **Project number:** 1F32CA253968-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Samantha Marie Fix
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,958
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066180

## Citation

> US National Institutes of Health, RePORTER application 10066180, Genetically engineering T cells to overcome the immunosuppressive melanoma microenvironment (1F32CA253968-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10066180. Licensed CC0.

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