City of Hope reports that it is the first institution in the United States to open an immunotherapy clinical trial for liver cancer that, if successful, eventually represents a transformative treatment of the often fatal disease into an outpatient procedure.
Patients with advanced hepatocellular carcinoma, the most predominant type of liver cancer, have a very poor prognosis and limited treatment options. The rate of liver cancer diagnoses has more than tripled since 1980, according to the American Cancer Society. About 42,030 new cases are expected and about 31,780 people are expected to die from the disease in 2019, reports City of Hope in a press release picked up by EurekAlert!
To improve survival rates for liver cancer, City of Hope physician-scientists have started a phase 1/2 research clinical trial that engineers a person’s own immune T cells to target an alpha fetoprotein (AFP)-peptide/HLA-A2 complex-a small protein/antigen highly expressed in hepatocellular carcinoma. It is secreted from liver tumor cells and is somewhat specific to that organ.
City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, is the first of five institutions in the United States to test Eureka Therapeutics’ experimental ET140202 ARTEMIS™ T cell therapy on patients who are AFP-positive and HLA-A2 positive. The goal is to create a true targeted approach to using immune cells to hone in on only tumors, and nothing else.
The patients who are selected for the clinical trial have metastatic or locally advanced, inoperable liver cancer and have failed or not tolerated at least one line of treatment for advanced hepatocellular carcinoma. The clinical trial tests for safety and tolerability of ET140202 T cells. If the initial study participants react favorably, the trial will move into drug efficacy testing. The study aims to assess patients for two years and to follow them for 15 years post-treatment.
The ongoing clinical trial further advances City of Hope’s portfolio of experimental treatments for advanced liver cancer. Now, City of Hope patients with liver cancer may not have to resort to standard treatments for their advanced disease until their fourth line of therapy. In total, City of Hope has 20 ongoing T cell and CAR T clinical trials.
Yuman Fong, MD, director of the Center for Surgical Innovation at City of Hope, co-investigator of the ongoing clinical trial and the Sangiocomo Family Chair in Surgical Oncology, noted, “The novel T cell platform has the potential to transform T cell therapy into an outpatient procedure.” He continued, “We, Eureka Therapeutics and others are designing T cell therapies with low toxicity.”
Principal investigator Daneng Li, MD, reports that “Traditional immunotherapy such as checkpoint inhibitors release the breaks on the immune system, which allows it to sometimes attack the tumor but can also lead to attacks on other parts of the human body.” Dr. Li mentioned “This approach engineers immune cells to directly attack a protein that is expressed on liver cancer. We are trying to individualize treatment of patients with advanced liver cancer.”
The Investigational Therapy
ET140202 T cell therapy was first tested in China in a first-in-human, proof-of-concept study. The ongoing study has demonstrated a favorable safety profile with no cytokine release syndrome (serious side effect that includes overexpression of certain proteins) or drug-related neurotoxicity (side effects).
The engineered ET140202 T cells recognize and bind to the AFP peptide/HLA-A2 complex, become activated and kill the liver tumor cells.
About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes, and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy, such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked one of America’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California.
Yuman Fong, MD, director of the Center for Surgical Innovation at City of Hope, co-investigator
Daneng Li, MD, co-principal investigator, medical oncologist
Stephen J. Foreman, director of the T Cell Immunotherapy Research Laboratory at City of Hope, co-investigator of the clinical trial and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation.