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T-Cell Receptors (TCRs) that Recognize and Eliminate Melanoma Cells

Novel approach to target melanoma & other solid tumors, and provides a roadmap to select TCRs for the next generation of cell therapies.

  • Therapeutics

Project Overview

  • T cell receptors (TCRs) are proteins that allow T cells to recognize and attack infected or cancerous cells.
  • Scientists at Dana-Farber have developed a technology to isolate tumor-specific TCRs that are capable of recognizing and eliminating tumor cells upon recognition of tumor antigens.
  • This technology is available for sponsored research and licensing.

Technology

The claimed invention is the possibility to isolate tumor-specific TCRs that are capable of recognizing and eliminating tumor cells upon recognition of tumor antigens. This relies on the identification of TCRs expressed by tumor infiltrating lymphocytes with an exhausted cellular state, as defined by the elevated transcriptomic or protein expression of molecules associated with T cell exhaustion (e.g. PD-1, CD39, etc). The identified TCR sequences are useful in adoptive T cell therapies to manipulate T cells and elicits a reaction against tumor cells by gene transfer of the identified TCRs. There are also method claims associated with this process which includes gene modification of T cells with other transgenes to control their reactivity. 

The lab discovered the antitumor reactivity of intratumoral CD8+ T cells for TCRs which are reactive to melanoma cells is linked with the phenotypes of exhaustion. This was discovered by performing single cell profiling of CD8+ T Cells from melanoma samples, developed by RNA/TCR sequencing and peptidome profiling, and then combining with reconstruction and specificity testing of hundreds of TCRs cloned from the same CD8+ T cells. This gave a clear understanding of the native state of melanoma T cell interactions in untreated tumors. 

By linking antigen-specificity to TCR clonotype and cellular phenotype of melanoma-infiltrating lymphocytes at single-cell resolution and at large-scale, the researchers showed that tumor specificity shapes the exhausted phenotype of tumor-infiltrating CD8+ T cells. 

Team Members: Catherine J. Wu, MD, Giacomo Oliveira, PhD

Applications

This novel approach allows researchers to target melanoma and other solid tumors, and also provides a roadmap for other researchers on how to select TCRs for the next generation of effective cellular therapies. 

Opportunities

This technology is available for sponsored research and licensing.

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