Selective Predators: Natural Killer T Cells Take Aim at Solid Tumors
While surgery, radiation therapy and chemotherapy are still considered mainstays in cancer treatment, many oncologists and researchers are looking to immunotherapy as a way to treat cancer patients.
Baylor College of Medicine has announced a major collaboration with biotech company Cell Medica, to develop advanced technology for genetically engineered immune cells designed to treat solid tumors.
“This is really quite an important scientific endeavor because we’re working with leading-edge technology,” said Gregg Sando, chief executive officer of the London-based Cell Medica, which has its U.S. headquarters in the Texas Medical Center. “There are current generation products that we could start using now, but the focus is to take this technology to another level and make it work much more effectively against solid tumors.”
The partnership aims to accelerate the pre-clinical research of Leonid Metelitsa, M.D., Ph.D., professor of pediatrics – oncology at Baylor College of Medicine. His research team is part of the Texas Children’s Cancer Center and the Center for Cell and Gene Therapy at Baylor and Texas Children’s Hospital. Metelitsa investigated chimeric antigen receptor (CAR)-modified natural killer T cells (NKT) as a safe and effective platform for cancer treatment.
In exchange for Cell Medica’s expertise in cell therapy manufacturing and commercialization, Baylor provided the company with exclusive rights to the proprietary NKT cell platform, five product candidates and the option to license additional future products. Clinical trials should begin within the next two years.
“This is an exciting development in the field of cancer immunotherapy,” Metelitsa said. “The joint program with Cell Medica provides a unique opportunity for me to see a real translation of my pre-clinical research into clinical practice. Without Cell Medica’s support, it would probably take us another five to 10 years to get there.”
In recent years, the scientific community has seen considerable success harnessing the power of immune cells, specifically T cells, against blood-related malignancies. This subtype of white blood cells is extracted from the patient and genetically engineered with CARs, which enable the T cells to identify antigens on tumor cells. Doctors then grow the T cells in the laboratory and infuse patients with the new and improved cells, boosting their immune systems with powerful cancer-fighting ingredients.
Currently, CAR T cells are limited to patients with blood cancers. But after moving to Baylor in 2009, Metelitsa realized that the same process—adding CARs to specialized immune cells with natural anti-tumor properties—could treat a larger, unmet population: solid tumor patients. More than 90 percent of all cancers are solid tumors, including breast, colon and lung cancers common in adults, and neuroblastoma, sarcomas and brain tumors in children, according to Metelitsa.
“That’s why there is such a big race to develop therapies that could be effective for solid tumors,” he said.
Because solid tumors are equipped with a toxic, protective shield that suppresses immune responses, the body’s white blood cells cannot recognize or attack the malignancy when it reaches the tumor, leaving the patient at the cancer’s mercy. Enter the natural killer T cells, highly selective predators adept at attacking solid tumors. These white blood cells have unique properties that give them the natural ability to localize to the tumor site and disable the tumor’s immunosuppressive response mechanism.
Like contemporary soldiers outfitted with advanced armor and special homing devices, genetically engineering NKT cells—carrying CARs and Interleukin 15, a protein that promotes NKT cell growth—are highly effective in targeting the tumor and fighting the toxic microenvironment surrounding it.
Using this next-generation technology, Baylor and Cell Medica will be able to target a range of cancers, including small lung cancer, liver cancer and triple negative breast cancer. Baylor fielded multiple offers from companies seeking to commercialize Metelitsa’s work before accepting a second partnership with Cell Medica. In 2011, Baylor worked with the biotech company on T cell immunotherapy for cancers associated with the Epstein-Barr virus.
“Since then, we’ve been able to accomplish a huge amount together,” Sando said. “We’ve got the advantage of two really good players working together, we were delighted to have the possibility of working with Baylor College of Medicine in a new collaboration.”
Baylor’s team, led by Andrew Wooten and Michael Dilling, Ph.D., helped structure the partnership. Under the direction of a joint steering committee, Baylor will oversee the first clinical trials. Meanwhile, Cell Medica will develop a manufacturing strategy and, after the first trials are complete, assume responsibility for taking the therapy to market.
While the Baylor and Cell Medica collaboration marks a pivotal point in the future of Metelitsa’s work, the partnership heralds a significant adjustment in the quest for a cancer cure.
“We are at the beginning of a paradigm shift in the way we treat cancer, and Houston’s certainly going to have an important role to play in how this immunotherapy industry shapes up in the years ahead,” Sando said.