Understanding the Immune Discovery that “May Treat All Cancer”

Harnessing the Immune System to Treat Cancer

The paper recently published by Cardiff University investigators revealed exciting but preliminary new information in cancer immunotherapy. Although at an early stage of discovery, this has significant potential and shows the benefits of supporting basic science research. Much more work is required for the findings published in Nature Immunology to be translated into treatments for patients, but every advancement continues to offer hope for finding cures for every child battling cancer.

To understand the findings of this paper and what it means for the future, here are a few things to know about the immune system, T cells, MR 1 and cancer:

Immune System as a Cancer Treatment:

Harnessing the immune system to fight cancer, or immunotherapy, are exciting and diverse cancer treatments that have revolutionized how we (at the MACC Fund Center at Children’s Wisconsin) treat many malignancies. Some immunotherapies help reveal cancer cells to the immune system, some stimulate current immune cells and others can even change or replace existing immune cells with new immune cells specifically targeting cancer. The potential promise of immunotherapy is an efficient targeted treatment with less side effects than conventional chemotherapy.

T Cells:

One type of immune cell is a T cell. There are many different sub types of T cells. Some carry out surveillance looking for viral infections or malignantly transformed cells. Once those T cells find their target, they cannot only destroy their target but also signal to the rest of the immune system to assist in the fight.

Understanding the Research Findings

Published in Nature Immunology: Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1 by Crowther, Dolton and colleagues.

They found a new clone or group/type of T cell that recognized cancer cells in a new way and then destroyed them. Excitingly, those T cells specifically destroyed multiple different types of cancer (lung, melanoma, prostate, breast, bone, ovarian, leukemia, and colon) but did not kill the healthy non-cancer cells that were tested. The group then used a technique called CRISPR-Cas9 to mutate the proteins in the cancerous cells in a number of ways. From this, they identified MHC class I-related protein MR1 as a candidate for how the cancer cells were identified. This MR1 is expressed on all cells in the body. MR1 is thought to present products of metabolism on the surface of cells. Critically, the recognition of those cancer cells was dependent on MR1 being present and interacting with the T Cells but was NOT targeting the MR1 itself. The T cells were targeting something complexed with MR1. The researchers were unable to identify what was actually being targeted, only that it was complexed with MR1.

What’s Next

While this is an exciting discovery, there is much to do before treatments for patients can be designed, tested and implemented. And there are still many questions to answer.

What is the actual target, or ligand complex, of this T cell sub type? Once there is a target identified – can we then alter a patient’s T cells to target that ligand? Can that target be treated with a non-T cell-based therapy? Is that target present on normal cell types that were not tested in the current study? Can the target also become expressed on normal, healthy, cells when they undergo different types of metabolism? Are there people who naturally have more of these T cell sub types that are resistant to cancer?

The reality is that plenty of work remains to treat the hundreds of types of existing cancers. However, childhood cancer researchers supported by the MACC Fund are well poised with the tools to implement treatments based on this target complex should it pan out through further study. With MACC Fund support, we already have been developing T cell-based immunotherapy treatments to safely and specifically target cancers in children and young adults. With your support, we are constantly attempting to develop treatments that are more effective and safer, so children with cancer become cancer survivors to enjoy a long, happy, and healthy life.

To support childhood cancer research, donate today: https://maccfund.org/donation/

Nathan J. Schloemer, MD

Assistant Professor of Pediatrics – Hematology/Oncology/BMT

Children’s Hospital of Wisconsin – Medical College of Wisconsin

Jeffrey A. Medin, PhD

MACC Fund Professor of Pediatrics and Biochemistry

Children’s Hospital of Wisconsin – Medical College of Wisconsin