The Multipronged MEL8 T Cell: Superior T-cell discovered in cancer survivors

• T cells lie at the heart of cancer immunotherapy, capable of detecting and eliminating tumor cells through precise antigen recognition. Recent findings revealed that the MEL8 T-cell clone—first described as a "multipronged" T-cell receptor—was originally discovered in a melanoma patient who achieved complete and lasting remission following TIL (Tumor-Infiltrating Lymphocyte) therapy.
• Unlike conventional T cells, MEL8 recognizes multiple HLA-A*02:01–restricted tumor antigens across different cancer types, revealing an exceptional form of cross-reactivity with strong therapeutic potential.

Uncovering Molecular Sensitivity

• To establish the foundation for visualizing TCR–pMHC interactions in real-time, we used pMHC production, CRISPR-Cas9–mediated TCR exchange, and biophysical assays such as DSF (Differential Scanning Fluorimetry) and anisotropy. These preparatory studies paved the way for supported lipid bilayer (SLB)-based experiments.
• This research aims to uncover the molecular sensitivity and specificity of the MEL8 TCR clone, providing crucial insight into how multipronged T cells achieve broad, yet precise, tumor recognition.