Potential to Accelerate Application of CAR-T Therapy to Other Solid Tumors
EMERYVILLE, Calif. & DUARTE, Calif. -Eureka Therapeutics Inc., a biotechnology company focused on developing novel T-cell immunotherapies for the treatment of solid tumors, and City of Hope, a world-renowned independent research and cancer and diabetes treatment center, announced today that they have reached agreement to conduct an open-label, dose-escalating Phase 1 clinical trial of ET1402L1-CAR, a potential CAR-T therapy for the treatment of hepatocellular carcinoma, the predominant type of liver cancer. ET1402L1 is a human antibody, identified from Eureka’s proprietary E-ALPHA® phage library, which selectively targets liver cancer cells overexpressing alpha-fetoprotein (AFP).
“We are pleased to be working with Eureka Therapeutics on this unique approach to treating liver cancer with CAR-T therapy” Tweet this
“The clinical trial agreement represents an important milestone for Eureka, as it provides a pathway for treating patients with liver cancer, and it supports our business objectives to develop ET1402L1-CAR in areas of significant unmet medical need,” said Cheng Liu, Ph.D., President and Chief Executive Officer of Eureka Therapeutics. “This is a significant step in demonstrating that CAR-T cell therapy can be successfully used to target a major histocompatibility complex (MHC) presented antigen in solid tumors.”
Intracellular antigens, which account for the most tumor-specific antigens, are inaccessible by conventional CAR-T therapy. Such antigens which include AFP, however, are processed into peptides and presented by the class I MHC on the surface of tumor cells. A 2017 study (DOI: 10.1158/1078-0432.CCR-16-1203), published by Eureka and City of Hope in Clinical Cancer Research, showed that ET1402L1-CAR T cells can recognize the AFP-MHC complex and launch a potent anti-tumor response, offering a promising new avenue for T cell therapy against solid malignancies.
“We are pleased to be working with Eureka Therapeutics on this unique approach to treating liver cancer with CAR-T therapy,” said principal investigator Yuman Fong, M.D., The Sangiacomo Family Chair in Surgical Oncology and chair and professor of the Department of Surgery at City of Hope. “CAR-T therapy has shown remarkable success with liquid tumors. However, the lack of cancer specific cell surface antigens has limited the use of CAR-T therapy to other cancers. The results of this study could have a wide range of applications in other difficult-to-treat solid cancers such as lung and prostate cancer, which have few cell surface markers that are tumor-specific.”
“City of Hope has accepted the challenge to bring leading-edge treatments to patients with liver cancer,” said investigator Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and director of City of Hope’s T Cell Immunotherapy Research Laboratory. “We are optimistic that CAR-T therapy can be an important component in treating patients with solid tumors, including liver cancer.”
The Phase 1 clinical trial will be led by Fong and Forman. Other collaborating investigators include Christine Brown, Ph.D., Heritage Provider Network Professor in Immunotherapy, John Kessler, M.D., John Park, M.D., Ph.D., Saul Priceman Ph.D., Shirong Wang, M.D., M.P.H., and Susanne Warner, M.D., all of City of Hope in Duarte, California.
About Liver Cancer
Liver cancer is the fifth most prevalent and third most lethal cancer worldwide, with incidence rates on the rise and limited treatment options. Hepatocellular carcinoma is the predominant type of liver cancer, affecting over 700,000 people each year worldwide. Alpha-fetoprotein (AFP) is overexpressed, specifically in liver cancer, making it an ideal target for chimeric antigen receptor (CAR) T cell immunotherapy. However, AFP is intracellularly expressed and secreted, and therefore, not targetable by conventional antibody-based therapies.
About Eureka Therapeutics Inc.
Eureka Therapeutics Inc. is a privately held biotechnology company, headquartered in the San Francisco Bay area, focused on developing first-in-class T cell immunotherapies for hematological malignancies and solid tumors. Its core technology platforms center around the discovery and engineering of fully human antibodies against intracellular targets via the MHCI complex. The company is developing a pipeline of novel cancer therapeutics targeting intracellular oncogenes.
For more information, visit the company’s website at www.eurekainc.com.
About City of Hope
City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 48 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of “America’s Best Hospitals” in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution.