New Immunotherapy Approach Found in “Superagonist” Interleukin-15 Complex

Published: Sep 13, 2018

Roswell Park trial identifies small, critical protein involved in anticancer immune response

  • ALT-803 is a complex containing IL-15, a promising immunotherapy agent
  • Study is first of its kind to investigate ALT-803 in cancer patients
  • Treatment enhances key population of cancer-fighting immune cells
     

BUFFALO, N.Y. — Immunotherapy has become a well-established approach to treating cancer, but a recent development shows that the immune response to cancer can be further enhanced using cytokines, small proteins that act as chemical messengers transporting information between different types of immune cells. The findings have been published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).

 A clinical trial led by Marc Ernstoff, MD, the Katherine Anne Gioia Chair of Medicine at Roswell Park Comprehensive Cancer Center, found that a drug complex containing one of these cytokines, interleukin-15 (IL-15), is both safe and well tolerated in patients with advanced solid tumors. Results of the study show that IL-15 plays a critical role in enhancing certain groups of immune cells involved in cancer therapy.

Nearly a decade ago, the National Cancer Institute picked IL-15 as the immunotherapy agent most likely to cure cancer. Since then, a great deal of laboratory research supports IL-15’s potential to trigger a cancer-fighting immune response, but its performance in clinical trials has been mixed, in part because drugs containing IL-15 are difficult to produce and don’t last long in the body.

To overcome these challenges, an IL-15-containing “superagonist” complex called ALT-803 was recently developed by Altor BioScience to stimulate the production of CD8+ “killer” T cells and natural killer cells, which are specialized immune cells that recognize and attack cancer cells. The Roswell Park clinical trial, which enrolled 24 patients with advanced, incurable solid tumors (including melanoma, renal cell carcinoma, non-small cell lung cancer, and head and neck cancer), sought to identify the most effective dose and route of administration of ALT-803.

Overall, this treatment was well tolerated, with mild side effects similar to those seen with other immunotherapies (such as fatigue, nausea, fever, and injection-site reactions). Although some patients responded better than others, all trial participants experienced substantial increases in the number of natural killer cells and modest CD8+ T-cell increases, showing that the complex activates the immune response against cancer, even in patients with advanced disease.

“Our findings highlight the critical role of IL-15 in enhancing subsets of immune cells in the body involved with cancer therapy,” says Dr. Ernstoff, the study’s senior author. “Immune-communicating molecules in combination with other treatments will likely play an increasing role in cancer treatment and represent a new and promising approach to immunotherapy.”

IL-15-containing drugs such as ALT-803 show great promise for use in combination with other immunotherapies, including vaccines, immune checkpoint inhibitors, antitumor antibodies, and adoptive cell therapies. The study’s initial results have inspired several new clinical trials investigating the true potential of this agent in a wide range of cancers, including B cell malignancies, ovarian cancer, bladder cancer and lung cancer.

The study, “Phase I Trial of ALT-803, a Novel Recombinant Interleukin-15 Complex, in Patients with Advanced Solid Tumors,” is available at clincancerres.aacrjournals.org. The trial was approved and monitored by the Cancer Therapy Evaluation Program (CTEP) as well as the investigational agent sponsor, Altor BioScience. The Melanoma Research Alliance provided additional funding.

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Roswell Park Comprehensive Cancer Center is a community united by the drive to eliminate cancer’s grip on humanity by unlocking its secrets through personalized approaches and unleashing the healing power of hope. Founded by Dr. Roswell Park in 1898, it is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. Learn more at www.roswellpark.org, or contact us at 1-800-ROSWELL (1-800-767-9355) orASKRoswell@roswellpark.org

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