SAN FRANCISCO and SOUTH SAN FRANCISCO, Calif. – The Parker Institute for Cancer Immunotherapy and Xyphos Biosciences today announced a collaboration to create universal CAR-T therapies to treat multiple cancer types using the company’s ‘convertibleCAR’® platform.
Using this type of cell therapy, researchers endeavor to program a patient’s own immune cells to attack tumor cells with greater specificity, and potentially lower toxicity, when directed to tumor antigens with separate targeting antibodies. Unlike the first generation of approved cell therapies, this technology aims to allow more controlled antigen recognition for greater responsiveness to the tumor environment.
“This new approach provides a way to switch CAR-Ts on and off, which we hope will translate to greater efficacy and safety,” said Jeffrey Bluestone, Ph.D., CEO and president of the Parker Institute. “This technology has the potential to be best-in-class and applicable to a wide array of solid tumor targets.”
“The Parker Institute represents the gold standard for supporting innovative new cancer immunotherapy technologies,” said Jim Knighton, CEO of Xyphos. “This important partnership will allow us to move our programs forward at a quicker pace, shortening the time to reach cancer patients.”
The first chimeric antigen receptor T-cells, or CAR-T cells, were approved by the U.S. Food and Drug Administration for blood cancer in 2017 against the target CD19, a type of receptor present on several types of blood cancer cells. However, there have been challenges both with relapse and in treating solid tumors.
Xyphos’ ACCEL™ technology is designed to conquer these common challenges in cell therapy, including relapse, side effects and lack of efficacy in solid tumors.
“With our approach we are improving CAR-T safety, with the goal of preventing tumor recurrence by enabling target switching and multiplexing, and broadening potential indications through deployment of convertibleCAR-T therapeutics,” said Kaman Kim, Ph.D., vice president of research at Xyphos and co-developer of the ACCEL platform.
How It Works
ACCEL™ (Advanced Cellular Control through Engineered Ligands) enables precise control of activity and targeting of Xyphos’ universal CAR-T cell, termed convertibleCAR-T. Xyphos’ convertibleCAR technology exploits a powerful immune surveillance pathway involving NKG2D receptors that are naturally present on different cell types within the immune system including natural killer (NK) cells, T-cells and some macrophages.
Through protein engineering, Xyphos engineered the natural NKG2D receptor to be inactive until activated by a proprietary bispecific antibody also engineered by Xyphos, called a MicAbody® protein. Once the MicAbody is introduced, one end binds exclusively to the inactive NKG2D receptors on the convertibleCAR-T cell, and when the other end of the MicAbody binds the antibody-targeted cell, the convertibleCAR-T cell aggressively attacks and destroys the targeted malignant cell.
The resulting platform enables a single NKG2D CAR-T cell therapy to be precisely controlled and targeted to any antigen-expressing cell of choice using one or more tumor-specific MicAbody proteins. Using bispecific MIC-effector fusions (MicAdaptor™ proteins), Xyphos can externally add critical functionality (e.g. cytokine stimulation, checkpoint blockade, cell ablation, imaging biomarkers) specifically to the Xyphos convertibleCAR-T cells.
During the initial phase of research, the Parker Institute and Xyphos will work together on building and evaluating CAR-T cell product candidates against a variety of cancer cell surface targets.
“Working with this universal convertibleCAR platform, we are aiming to design and test new CAR-T therapies to help a wider group of cancer patients and ideally treat tumors that have so far remained resistant to CAR-T therapy,” said Fred Ramsdell, Ph.D., vice president of research at the Parker Institute.
About Parker Institute for Cancer Immunotherapy
The Parker Institute for Cancer Immunotherapy brings together the best scientists, clinicians and industry partners to build a smarter and more coordinated cancer immunotherapy research effort.
The Parker Institute is an unprecedented collaboration between the country’s leading immunologists and cancer centers. The program started by providing institutional support to six academic centers, including Memorial Sloan Kettering Cancer Center, Stanford Medicine, the University of California, Los Angeles, the University of California, San Francisco, the University of Pennsylvania and The University of Texas MD Anderson Cancer Center. The institute also provides programmatic support for top immunotherapy investigators, including a group of researchers at Dana-Farber Cancer Institute, Robert Schreiber, PhD, of Washington University School of Medicine in St. Louis, Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, Philip Greenberg, MD, of the Fred Hutchinson Cancer Research Center, and Stephen Forman, MD, of City of Hope.
The Parker Institute network also includes more than 40 industry and nonprofit partners, more than 60 labs and more than 170 of the nation’s top researchers focused on treating the deadliest cancers. The goal is to accelerate the development of breakthrough immune therapies capable of turning most cancers into curable diseases. The institute was created through a $250 million grant from The Parker Foundation.
About Xyphos Biosciences Inc.
Xyphos, a privately held development-stage biotechnology company, is focused on the creation and development of immuno-oncology therapeutics designed to harness the power of a patient’s immune system to cure cancer. Xyphos’ novel and proprietary ACCEL (Advanced Cellular Control through Engineered Ligands) technology platform allows new and potentially better ways to mobilize and control engineered immune cells to find and destroy cancer cells throughout the body. Applying the platform, the patient’s own immune cells are re-programmed to express a universal Chimeric Antigen Receptor (CAR) which enables the delivery to those therapeutic cells various classes of controlling and modulating agents, including antibodies, cytokines and kill functions. The resulting convertibleCAR-T cells can be specifically directed to tumor cells and their activity towards tumor destruction can be tightly controlled, potentially leading to safer and more efficacious treatments. Xyphos’ first convertibleCAR-T cell product candidate is in preclinical development and is scheduled to be tested in a first-in-human clinical study in early 2020. The company is headquartered in South San Francisco, CA. For more information on Xyphos, please visit the company’s website at www.xyphosinc.com.
ACCEL™, MicAbody®, MicAdaptor™ and convertibleCAR® are trademarks of Xyphos Biosciences Inc.
Parker Institute for Cancer Immunotherapy
Angela Bitting (media)