The development of an experimental gene-targeting therapy in cancer treatment that could be approved for the U.S. market this year was sparked in large part by the research funding support of a Stamford nonprofit.
The chimeric antigen receptor T-cell (CAR-T) drug, labeled tisagenlecleucel by its manufacturer, Novartis, in July was unanimously recommended for approval by the oncologic drugs advisory committee of the U.S. Food and Drug Administration. If the FDA grants final approval as expected this fall, it will be the first drug treatment targeting human genes approved for the U.S. market.
In Stamford, the Alliance for Cancer Gene Therapy since 2004 has provided a total of $1.8 million to Dr. Carl June at the University of Pennsylvania, the lead researcher in developing the CAR-T therapy. John E. Walter, president and CEO of the Stamford organization, said June’s work has helped to redefine perceptions of what gene therapy can accomplish.
“Oftentimes, gene therapy is perceived as taking the bad genes out and putting some good genes in,” Walter said. “In this case, a patient’s T-cells are being removed and re-engineered with a virus and reintroduced in the body. With this genetic re-engineering, they become killer T-cells — they go in and go after and kill the cancer cells.”
“Cancer cells in your body multiply and don’t know how to die,” said Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci. “We have cells in our system all of the time that are growing and dying, but cancer cells don’t do that. This therapy is for supercharging your own immune system to recognize these cancer cells and kill them.”
If approved, the Novartis drug would mark a milestone achievement for the Alliance, whose creation in 2001 was driven by a tragic loss caused by cancer in its co-founders’ family. Edward Netter, chairman and CEO of Geneve Corp., a financial services holding company in Stamford, and his wife Barbara, a staff therapist at Pelham Family Services in Westchester County, lost their daughter-in-law, Kimberly Lawrence-Netter, to breast cancer. Edward Netter died from cancer in 2011. His wife serves as the nonprofit’s honorary board chairwoman.
Walter, who served as CEO of the Leukemia & Lymphoma Society before joining the Alliance in May 2016, noted that this organization differed from most because all of its raised funds are used solely to finance research. “Our administrative expenses are paid for by our board and by the Netters,” he said, and the nonprofit’s four-person staff works out of Geneve Corp. headquarters. “One hundred percent of your contributions go to research.”
Since its founding, the Alliance has allocated approximately $29 million in grants to U.S. and Canadian projects. “These are grants to two different types of scientists,” said Cianci. “We started funding young investigators at assistant professor level who have just become independent. It is difficult for them to get funding, especially in an area as innovative as gene therapy, and the government doesn’t like to fund what they see as high-risk projects. We also fund clinical investigators, which included Dr. June.”
The Alliance puts out two requests for funding applications each year, which are judged through a peer-review process coordinated by a scientific advisory committee.
“There is always more research than there are dollars,” said Walter. “Invariably, we are leaving research on the table because we don’t have the dollars to fund those.”
The nonprofit itself receives funding through contributions from longtime donors and an annual fundraising event coordinated by Swim Across America that is held in the Long Island Sound directly across from its offices. “That raises about $400,000 a year,” Walter said.
Dr. June’s Alliance-funded research was published in a medical journal in 2011 in a study of three patients with advanced chronic lymphocytic leukemia. Novartis, the Swiss pharmaceutical company, expressed interest in the results and paid the University of Pennsylvania $20 million to license the technology.
“Once we have survival data for these patients” in Novartis-sponsored clinical trials, “over time the FDA could consider using this as frontline treatment instead of highly toxic chemotherapy,” said Walter.
For Cianci, the Alliance’s mission is crucial in encouraging new generations of researchers to focus on cancer and gene therapy solutions, especially when federal funding is being threatened by budget cuts.
“If we don’t fund the young scientists, they are going to leave the field,” she warned. “We don’t want to lose some of these incredible minds. The average age for getting your first grant from the National Institute of Health is 42. What do you tell someone who just became a postdoctoral researcher and wants to have their own lab? How are they going to get funding?”
“One in four people could potentially get cancer in their lifetimes,” Cianci said. “And who hasn’t been touched by cancer in one way or another?”