NIH researchers report success with new immunotherapy approach to cancer

National Cancer Institute scientists demonstrate progress in treating woman with rare epithelial cancer type, using immune cells that recognize and attack her tumor.

by John Tyburski

Copyright © Daily Digest News, KPR Media, LLC. All rights reserved.

Firstpublished at Daily Digest News on May 8, 2014

Researchers at the National Institutes of Health’s National Cancer Institute (NCI) reported this week that they are seeing progress in treating a rare form of cancer in a 43-year-old woman using her own immune cells that recognize and attack the cells of her tumor. This new cancer immunotherapy approach, described in a report published on May 9 in Science, provides evidence that certain immune cells in humans can identify and attack mutant proteins of cancers that develop from epithelial cells. By growing vast numbers of these immune cells and putting them back into the body of the patient, researchers are giving this natural defense system a substantial boost.

Epithelial cells line exterior and interior surfaces of the body. Many types of common cancer and some rare forms arise from epithelial cells, and these cancer cells have a number of genetic mutations that can translate into mutant proteins. Some mutant proteins can trigger anti-tumor immune responses. Earlier work by Steven A. Rosenberg and colleagues at the NCI showed a certain type of immune cell infiltrates and is reactive to mutations in melanoma cells. These immune cells, called tumor-infiltrating lymphocytes, “learn” to recognize the mutant proteins on cancer cells and attack the cancer cells in much the same way the immune system fights off foreign invaders. This phenomenon forms the basis for adoptive cell therapy (ACT) used in treating melanoma.

“Our study deals with the central problem in human cancer immunotherapy, which is how to effectively attack common epithelial cancers,” said Rosenberg, chief of the Surgery Branch in NCI’s Center for Cancer Research. “The method we have developed provides a blueprint for using immunotherapy to specifically attack sporadic or driver mutations, unique to a patient’s individual cancer.”

In the present study, researchers first used whole-exome genetic sequencing to identify any mutations in the patient’s cancer cells that her immune cells might recognize. A potential target, a protein called ERBB2-interacting protein (ERBB2IP), was found along with TILs from the patient that recognize it. Approximately 42.4 billion TILs were then grown and transferred into the patient, of which about 25% could recognize ERBB2IP. After another followup treatment with an enriched anti-ERBB2IP TIL preparation, ongoing shrinking of the tumors was observed.

“Given that a major hurdle for the success of immunotherapies for gastrointestinal and other cancers is the apparent low frequency of tumor-reactive T cells, the strategies reported here could be used to generate a T-cell adoptive cell therapy for patients with common cancers,” said Rosenberg.