A new study advocates that cancer cells become vulnerable to immunotherapies due to mutations that stop the cells from proof reading their DNA.
Cancer was controlled in 77 percent of patients with defects in DNA mismatch repair, by a type of immune therapy known as PD-1 Blockade. Through this system the cells proof read and repair errors in DNA. PD-1 blockade therapy was effective against 12 different types of hard tumors, including colorectal, gastroesophageal and pancreatic cancers, and even tumors of unidentified source, researchers report in Science.
Richard Goldberg, study coauthor and an oncologist at West Virginia University Cancer Institute in Morgantown said that where the tumor started did not matter, but what mattered the most is why the tumor was started.
Mutations build up in cells of people with defective DNA proof readers, which can lead to cancer. While mismatch repair errors can spark cancer, they may also be its Achilles’ heel: Some misspellings cause the cancer cells to construct strange proteins that the immune system uses to target tumors for destruction.
The researchers found that even before the treatment was initiated the cancer patients picked up for the study showed symptoms of certain infections and tumor-fighting T cells
that target these strange proteins in their body. Kellie Smith, coauthor and a cancer immunologist at Johns Hopkins University said treatment with antibody pembrolizumab(brand name Keytruda) caused these T cells to increase in number.A protein called PD-1 receptor is present on the surface of T cells to which the antibody pembrolizumab attaches. Some tumor cells use this PD-1 receptor to hide from the immune system. Blocking the receptor with the antibody unveils the tumors. As a result, Smith expressed that immune cells could go to all corners of the body and eradicate tumors. This also includes seeking disgracefully lethal metastatic tumors — ones that have spread from other parts of the body. Once the T cells are in position for action, they may travel around the body for a long time, preventing cancer from clinging again.
86 patients participated in the study and all had metastatic cancers that had not reacted well to other treatments. For 18 patients, the treatment with pembrolizumab appeared to cure them completely. Their tumors vanished completely. Following two years of treatment, 11 of those patients were withdrawn off the antibody. Their tumors have not reverted even after an average of 8.3 months.
For other patients the tumors shrunk but didn’t disappear. It remained stable during and after treatment. Goldberg said that the scans revealed that some of the patients still had tumors, but biopsies showed no remaining cancer cells. The so called “tumors” are indeed clusters of immune cells that have invaded sites to kill cancer, he says.
Everyone did not fare well. Tumors in five patients shrunk in the beginning, but then began to develop again. DNA from three of those people were analyzed and showed that two had developed mutations in the beta 2-microglobulin gene, which helps immune cells track down their targets.
Ill effects of this treatment included skin rashes, thyroid problems and diabetes as the therapy caused auto immunity to some extent.
Revving up the immune system to battle against a wide variety of tumor types may take cancer therapy to new heights. In recent years, scientists have formulated drugs to aim specific mutations in one type of cancer. “That’s old school,” Immunotherapy “is the future.” says Khaled Barakat, a computational scientist at the University of Alberta in Canada.
FDA approved pembrolizumab on May 23rd 2017 for advance-stage cancer patients with mismatch repair mutations for whom other lines of treatments have failed. The researchers approximate that about 60,000 late-stage cancer patients each year could be eligible for the immune therapy, in the US.
