Research from Bloomberg-Kimmel Institute Among Best of #ASCO2017

More than 20 years ago, when Johns Hopkins scientists Bert Vogelstein, Ken Kinzler and their colleagues linked certain cancers to mutations in genes that repair DNA, they may not have imagined that their findings would spark an idea that has become a crystal ball for predicting whether immunotherapy is more likely to work in a person with cancer.

The idea, featured in the American Society of Clinical Oncology's Clinical Advances 2017, began four years ago at a meeting between Vogelstein and scientists at the Bloomberg~Kimmel Institute for Cancer Immunotherapy to figure out why a single patient with colon cancer had responded to an immunotherapy drug and 15 others with colon cancer had not. What was different in that single patient? The scientists had a hunch that tumor cells in the lone responder had more mutations than those of the other patients. More mutations trigger the production of more abnormal proteins, which appear foreign to the immune system. These mutation-ridden tumor cells are more visible to the immune system than tumors with fewer mutations, and immunotherapy may be much more likely to work in these patients.

The hunch paid off, and when the scientists sequenced the patient's tumor, they found mutations in a set of genes, called "mismatch repair," which work to mend DNA mistakes. Bloomberg~Kimmel Institute scientists organized a clinical trial of patients with and without mismatch repair mutations and presented and published initial results in 2015. The trial was expanded and more results were presented in 2016 showing high response rates to the immunotherapy drug pembrolizumab among patients with many types of cancer who carry mismatch repair mutations. Bloomberg~Kimmel Institute experts estimate that 20,000 new patients who carry mismatch repair mutations are diagnosed each year in the U.S.

One of those patients is Stefanie Joho. Given a death sentence and no hope, Stefanie came to Johns Hopkins looking for a therapy that could buy her time. She enrolled in the Bloomberg~Kimmel Institute clinical trial and is now in complete remission. Listen to Stefanie's experience with immunotherapy:


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