Behind the new kind of cell therapy that just won FDA approval

21 Feb 2024
www.biopharmadive.com
Cell TherapyImmunotherapyPhase 3Phase 2Gene Therapy
A long research journey has finally paid off for Iovance Biotherapeutics, which last week won Food and Drug Administration approval of the first cell therapy to treat advanced melanoma. The clearance could also open the door for a new type of cancer immunotherapy.
Iovance’s therapy, called Amtagvi, is built from a type of immune cells known as tumor-infiltrating lymphocytes, or TILs, which are collected directly from a tumor sample and fortified in a laboratory to better fight the cancer.
Academic researchers have studied TIL therapy for decades, but scientific and regulatory factors slowed the technology’s progress toward market, according to Jason Bock, head of the Cell Therapy Manufacturing Center and an expert on TIL therapy.
“This is the first cell therapy modality that has shown good results in solid tumors,” he said.
While CAR T-cell therapies can be powerfully effective in blood cancers, they haven’t performed as well in solid tumors. A one-time treatment, TIL therapy holds the potential to durably treat some of these solid tumors — some treated patients have been cancer-free for a decade or more, Bock said.
Behind the new kind of cell therapy that just won FDA approval
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Source: BioPharmaDive
Jason Bock, CEO of Cell Therapy Manufacturing CenterPermission granted by CTMC
Amtagvi will cost approximately $515,00 per patent before rebates and discounts. The FDA approved the therapy based on Phase 2 data, and is requiring Iovance confirm those results with a Phase 3 confirmatory trial. The drug’s indication is limited to people with melanoma that can’t be surgically removed or has spread, and was previously treated with other drugs.
Others could follow Amtagvi, too. “It will blaze this trail for others to follow on with enhanced next-generation products,” said Bock. “I think those will be where we really see some dramatic impacts of TIL in the overall treatment of solid tumors.”
Harnessing the immune system
Eligible patients receive Amtagvi in select treatment centers, from where TILs are extracted and sent to a manufacturing center. There, they are isolated, grown and filtered before being sent back to the treatment center.
The patient undergoes lymphodepletion to kill existing T cells before doctors infuse them with billions of the beefed-up cells, accompanied by a short course of high-dose Proleukin, an interleukin-2 product Iovance acquired in 2023. The IL-2 helps the infused cells transition from the controlled laboratory environment into the body, Bock said.
Treatment can result in low blood counts, infection and other organ-related complications that can be serious — risks the FDA highlighted in a black box warning. The accompanying IL-2 regimen can bring its own risks, too.
“[High-dose IL-2] carries its own toxicities and is a difficult treatment for patients to handle,” Bock said.
Companies developing second-generation TIL treatments are working on alternatives to IL-2, which could reduce side effects. The lymphodepletion process may also be problematic. In December, the FDA placed a clinical hold on an Iovance lung cancer trial after a patient died, potentially related to this process.
A difficult development road
One reason it took so long to bring a TIL treatment to market is due to one of its cancer-fighting strengths, Bock said.
Unlike CAR-T -cells, which have to be engineered, the body naturally deploys TILs to infiltrate a tumor’s layers. The challenge is that TIL cells can get “beaten down” in the process, according to Bock, and the tumor evolves to avoid or repress them.
“They don’t have the fortitude to contain the cancer. So, the goal [with TIL therapies] is to enhance and multiply them to turn them into an army capable of a successful attack,” Bock said.
TILs are polyclonal and can recognize many targets on cancer cells. While that makes them attractive as a treatment choice, it also created regulatory hurdles. The FDA had to hammer out a way to regulate this new kind of drug without a predefined target, Bock said.
TILs in the pipeline
Several other TIL treatments are currently in the pipeline. Many also target melanoma.
In theory, though, TILs have the potential to work against a broad range of solid tumors. For the next generation to be effective in other cancers, better manufacturing methods will be needed, Bock said.
While much of the work on TILs still happens in academic research centers, several companies — such as Turnstone Biologics, Lyell and Instil Bio — are testing second-generation TILs against targets including breast, colorectal and ovarian cancer. Iovance is studying its therapies in cervical cancer, non-small cell lung cancer, and head and neck squamous cell carcinoma.
With Amtagvi’s approval, Bock predicts investment in TILs will surge, much like it did when the FDA approved the first CAR-T cell treatment.
“It's hard to be the first, but what's exciting is that after you're done with the first there's a trail there for others to build upon and improve upon,” Bock said.
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