MR1 as a Broad Signature of Cancer, Suitable for T Cell Targeting
Meaningful progress towards the control of cancer, ending it as a major threat to life and health, will be led by programs that can produce very broadly applicable treatments. That means therapies that can be applied to many (or even all) cancers with minimal differences in configuration or need for further per-cancer development. There are hundreds of cancer subtypes, but only so many researchers, and only so much funding for research and development: development of highly specific therapies is just not an effective path forward.
Examples of the most promising lines of work with broad application include the OncoSenX suicide gene therapy targeting p53 expression, interference in telomere lengthening, and blocking immune inhibitors such as CD47 that cancer cells use to evade the immune system. Researchers here report on another possible approach, a very broad cell surface signature of cancer that might be used to build chimeric antigen receptor T cell immunotherapies that can be applied to a very wide range of cancers indeed.
T-cell therapies for cancer - where immune cells are removed, modified and returned to the patient's blood to seek and destroy cancer cells - are the latest paradigm in cancer treatments. The most widely-used therapy, known as CAR-T, is personalised to each patient but targets only a few types of cancers and has not been successful for solid tumours, which make up the vast majority of cancers. Researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognises and kills most human cancer types, while ignoring healthy cells. This TCR recognises a molecule present on the surface of a wide range of cancer cells as well as in many of the body's normal cells but, remarkably, is able to distinguish between healthy cells and cancerous ones, killing only the latter.
Conventional T-cells scan the surface of other cells to find anomalies and eliminate cancerous cells - which express abnormal proteins - but ignore cells that contain only "normal" proteins. The scanning system recognises small parts of cellular proteins that are bound to cell-surface molecules called human leukocyte antigen (HLA), allowing killer T-cells to see what's occurring inside cells by scanning their surface. HLA varies widely between individuals, which has previously prevented scientists from creating a single T-cell-based treatment that targets most cancers in all people. The new study describes a unique TCR that can recognise many types of cancer via a single HLA-like molecule called MR1. Unlike HLA, MR1 does not vary in the human population - meaning it is a hugely attractive new target for immunotherapies.
T-cells equipped with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells, while ignoring healthy cells. To test the therapeutic potential of these cells in vivo, the researchers injected T-cells able to recognise MR1 into mice bearing human cancer and with a human immune system. This showed "encouraging" cancer-clearing results which the researchers said was comparable to CAR-T therapy in a similar animal model.
Couldn't you also use antibodies to MR1? These are available.
Dr. P