FDA approves first one time cell therapy for a solid tumor

FDA approves first one-time cell therapy for a solid tumor

Iovance Biotherapeutics_company with kind permission

Pictured: The Iovance Cell Therapy Center/courtesy of Iovance Biotherapeutics

On Friday, the FDA approved Iovance Biotherapeutics' lifileucel as the first one-shot cell therapy for a solid tumor and the first tumor-infiltrating lymphocyte (TIL) therapy.

Amtagvi, as lifileucel is known commercially, was approved under the FDA's accelerated approval process, which allows approval of drugs for serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit.

“The approval of Amtagvi represents the culmination of scientific and clinical research efforts leading to a novel T-cell immunotherapy for patients with limited treatment options,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.

About 8,000 people in the U.S. die from melanoma each year, according to Iovance's regulatory filing. “The approval of Amtagvi provides hope for those with advanced melanoma who have progressed after initial standard therapies, as current treatment options are not effective for many patients,” said Samantha R. Guild, president of AIM at the Melanoma Foundation, in an opinion.

Amtagvi is approved for autologous use only and carries a warning for treatment-related mortality, persistent severe cytopenia, serious infections, and cardiopulmonary and renal impairment.

Speaking to BioSpace ahead of the approval, experts said it would give the space a much-needed boost.

“It's been a long time coming, but approval would clearly confirm the progress in this area, and we expect this to increase rapidly from now on,” said Lynn Seely, CEO of Lyell, a company that produces TIL and CAR systems. T is developing clinical-stage therapies, BioSpace said.

40 years in the making

It took almost four decades for TIL technology to mature. The method was developed in 1982 by Steven Rosenberg and colleagues at the National Cancer Institute using mouse cells; They used the method on melanoma patients in 1988 and the treatment has shown great effectiveness in treating advanced melanomas in animal experiments and clinical trials.

TIL therapies utilize the patient’s own immune cells – lymphocytes – which tend to be suppressed in the tumor environment. These cells can be extracted from tumor biopsies, increased in number or remodeled for greater efficacy, and then transfused back into the patient, resulting in antitumor activity.

“The very fact that these lymphocytes found their way into the tumor environment suggests this [they] “I recognized something important in the tumor” and can effectively fight it, said Madan Jagasia, CEO of Obsidian Therapeutics, which is developing genetically modified TIL therapies.


Although CAR-T therapies have changed the way blood cancers are treated, their use against solid tumors, which account for 90% of all cancer cases worldwide, has proven more difficult.

Part of the appeal of TIL therapies lies in their ability to recognize multiple antigens simultaneously, something CAR-Ts are unable to do. Conventional CAR-T can only recognize a small number of proteins on the surface of tumor cells, while TILs can identify tumor targets derived from intra- or extracellular tumor proteins, said Sammy Farah, CEO of Turnstone Biologics, a clinical-stage biotech company , which is engaged in developing TIL therapies for breast and colorectal cancers as well as uveal melanoma. He added that TILs are likely to be successful as a treatment modality because solid tumors are known to be heterogeneous.

Go new ways

While more than 75 TIL immunotherapies are in preclinical or clinical trials for various indications, melanoma has been the poster child for this area, and Iovance is the first company to reach the finish line with a TIL therapy for advanced disease.

“There are no FDA-approved options for advanced melanoma under the current standard of care,” Friedrich Graf Finckenstein, Iovance's chief medical officer, told BioSpace before the approval, adding that the company was confident in lifileucel's potential, “that “To redefine the treatment paradigm for these cases.” Patients.”

Iovance completed its ongoing BLA application to the FDA in March 2023, supported by clinical data showing that lifileucel produced an objective response rate of 31% at an average of 36.5 months, with 42% of the response rates lasting two years or longer.

“TIL, a cell therapy, offers the potential for long-term healing responses that small molecules do not,” said Jason Bock, CEO of CTMC, a joint venture between Biotech Resilience and MD Anderson Cancer Center. Lifileucel will be particularly important for the nearly 50% of patients for whom checkpoint inhibitors have not worked, Bock added.

Tanisha Jackson, scientific program director for the Melanoma Research Alliance, agreed. “Not only is this beneficial for melanoma patients, we also expect TIL therapy to have broader implications for the treatment of many other types of cancer.”

Scaling challenges

While this is a big win for the industry, experts see several challenges to expanding manufacturing. Production time for TIL is about four to six weeks, Lyell's Seely said. Shorter culture time is associated with improved cell quality, functionality and positive clinical outcomes in patients with metastatic melanoma, a goal that Lyell says she wants to achieve. “We are continuing to develop new manufacturing protocols that aim to shorten the duration of TIL culture to less than three weeks without compromising the quality of TIL,” she shared. Meanwhile, Farah added that patient-to-patient variation is arguably the biggest challenge in scaling manufacturing.

Bock believes that the cost of TILs will remain high until the issues related to scaling production are resolved. “It is one of the most complicated therapies. Only after we figure out how to scale production and the processes to make these products [that] We can expect costs to come down,” he said.

However, Iovance does not anticipate any manufacturing problems, Chief Operating Officer Igor Bilinsky told BioSpace earlier this month, adding that the company has reduced the manufacturing time for lifileucel from six weeks to 22 days. The company established its first central cell therapy center in Philadelphia in 2021 to keep pace with potentially increasing demand.

Meanwhile, Jackson noted that there are several unknowns regarding the cost of TILs that could impact access to these therapies. “We don’t know what the therapy is for, how insurance companies will cover it, and what kind of patient assistance programs will be put in place,” she said.

Potential beyond melanoma

In addition to melanoma, Iovance has begun studying the potential of TIL in other solid tumor types, including metastatic non-small cell lung cancer (NSCLC) and gynecologic cancers, Bilinsky said. Lyell is also testing its TIL therapy in NSCLC, which Seely says is more difficult to treat than melanoma.

“Some of the hardest-to-treat cancers, which are less inflammatory and have a lower mutational burden, may also represent prime targets for TIL therapy,” Farah added.

Meanwhile, Obsidian genetically modifies TILs to limit the side effects experienced by patients. The company's lead candidate for melanoma produces a membrane-bound cytokine, IL-15, against a secreted cytokine to reduce the toxicity associated with high-dose IL-2 delivered with conventional TILs.

As companies continue to develop TILs for various indications, Bock said the approval “will usher in an entirely new wave of innovation to treat all solid tumors.”

Aayushi Pratap is a New York-based health and science journalist and a graduate of Columbia Journalism School. Reach her on LinkedIn.