# Targeting CTNNB1-S37F: TCR-T Cell Therapy for Solid Tumors
> Discover how engineering T cells to target the public driver neoantigen CTNNB1-S37F offers a new precision immunotherapy approach for solid tumors.

Tags: tcr-t-cell-therapy, neoantigens, ctnnb1-s37f, cancer-immunotherapy, precision-medicine, solid-tumors, oncology
## Targeting CTNNB1-S37F: A Public Driver Neoantigen
*   Focus: Engineering T cell therapy for solid tumors using shared (public) driver mutations.

## Background: Neoantigens & T Cell Therapy
*   Tumors carry somatic mutations producing neoepitopes.
*   Strategy: Shifting from patient-specific (private) to shared (public) antigens.

## How T Cells See Tumors
*   T cells recognize peptides bound to HLA (Human Leukocyte Antigen).
*   Driver mutations like CTNNB1-S37F are essential for cancer growth and uniformly expressed.

## Why CTNNB1 / β-Catenin?
*   Mutated in ~3.2% of all cancers.
*   Hotspot mutation in exon 3 prevents protein degradation, leading to oncogenic signaling.

## The Key Mutation: S37F
*   S37F is a recurrent hotspot generating high-affinity peptides for HLA-A*02:01 and HLA-A*24:02.
*   Mass spectrometry confirmed physical presentation on tumor cells.

## Engineering S37F-Specific TCR-T Cells
*   TCRs (TCRA2-2 and TCRA24) were identified from healthy donors to avoid immune tolerance.
*   The engineered cells specifically recognize mutant peptides while sparing wild-type cells.

## In Vivo Efficacy: Complete Eradication
*   Tested on Melanoma and Endometrial Adenocarcinoma models.
*   Results: 100% tumor-free early; long-term survival in 6/7 mice.
*   Organoids also showed eradication with low exhausting biomarkers (PD-1, TIM-3).

## Limitations & Precision Medicine
*   HLA restriction: Benefits subsets of patients with A*02:01 or A*24:02 alleles.
*   Scale: Approximately 3,885 patients/year in the US could benefit from this specific target.
*   Future goal: "Off-the-shelf" TCR-T libraries for various shared driver mutations.
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