Good news! Cancer is history (soon)! What, we are even discovering new super killer T-cells?
"Scientists have discovered a previously unknown type of immune cell that develops in people who successfully fight off cancer. Unlike other killer T cells, these home in on multiple cancer-associated targets at once, preventing new tumors forming for up to a year later and could lead to more effective cancer therapies. ...
The researchers focused on patients that successfully cleared their cancer after the treatment. They exposed blood samples from patients to tumor cells that had previously been taken from the same patient, and found that the survivors’ killer T cells still showed very strong responses even a year after entering remission.
They used algorithms designed to predict which targets these T cells were recognizing, based on differences between healthy and cancerous cells. And to their surprise, the scientists discovered that the cancer-defeating patients’ T cells were recognizing multiple protein changes in the cancer cells. In contrast, each T cell is usually thought to only target one protein at a time. ..."
In the new study, researchers ... investigated what biological differences there could be between successful and unsuccessful rounds of treatment in different patients. Over a decade they followed a phase I and II clinical trial examining what’s known as Tumor-Infiltrating Lymphocyte (TIL) therapy, which focuses on the white blood cells that are already at work in the patient’s tumor.
They used algorithms designed to predict which targets these T cells were recognizing, based on differences between healthy and cancerous cells. And to their surprise, the scientists discovered that the cancer-defeating patients’ T cells were recognizing multiple protein changes in the cancer cells. In contrast, each T cell is usually thought to only target one protein at a time. ..."
From the highlights and abstract:
"Highlights
• Individual T cells from successful immunotherapy recognize multiple cancer types
• A deciphering pipeline identifies new epitopes recognized by these “orphan” T cells
• Single T cells recognize multiple, different tumor-associated antigens simultaneously
• “Multipronged” TCRs exhibit superior cancer recognition compared with monospecific TCRs
Summary
The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such “multipronged” T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies."
Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy (open access)
Graphical abstract:
No comments:
Post a Comment