[Test]With 75 Pipeline Candidates, TIL Therapies Gain Momentum in Solid Tumor Space

With one approved therapy in the US and approximately 75 more in the pipeline, tumor infiltrating lymphocyte (TIL) treatments are a promising new approach to cancer immunotherapy, particularly for solid tumors that have proved resistant to other forms of treatment.

Unlike CAR-T therapies, which have achieved significant success in blood cancers but struggled with solid tumors, TIL therapies harness the power of cancer-fighting immune cells already present within tumors. However, these treatments face unique manufacturing, regulatory and commercial challenges that will need to be addressed to reach their full potential.

How TIL Therapies Work

TIL therapies employ a patient’s own immune cells that have already infiltrated their tumor tissue. These cells are particularly well-suited to treat solid tumors, as they are polyclonal, targeting multiple antigens. The cells are extracted during surgery, expanded and activated in a laboratory, and then reinfused into the patient to attack the cancer.

The approach was pioneered at the National Cancer Institute, where the process of extracting tumor samples, expanding the TILs, and reinfusing them was developed. Then, in February 2024, Iovance Biotherapeutics’ Amtagvi (lifileucel) became the first FDA-approved TIL therapy, receiving accelerated approval for adults with melanoma that has spread or cannot be removed by surgery and has been treated with other therapies.

First Approval Paves The Way

What Iovance has done with its approval “is pretty groundbreaking in terms of bringing a new type of therapy to market,” Anshul Mangal, president and CEO of Project Farma, a consulting firm providing biomanufacturing strategy and execution, told In Vivo. “There are a host of challenges of launching a therapy, a first of its kind, in a new class. They established the groundwork for clinical trials in this field, for manufacturing, for pricing, reimbursement, training and development.”

Specifically, Iovance persuaded the Food and Drug Administration to accept accelerated approval based on a single-arm trial, results of which showed a 31% response rate in patients with refractory melanoma, with over 40% of responding patients maintaining their response for more than two years.

That length of response is “deeper and more durable” than what has been seen with CAR-T,” Harpreet Singh, chief medical officer at global clinical research organization Precision for Medicine and a former FDA regulator in oncology, told In Vivo.

Iovance still needs to complete confirmatory trials to verify clinical benefit and receive full approval.

Manufacturing Hurdles And Progress

One of the most significant challenges TIL therapy manufacturers will need to overcome to widen use of the approach is to shorten manufacturing time. Under the original National Cancer Institute protocol, it took four to six weeks to produce a therapeutic amount of TILs. That significantly limited application of TILs to patients stable enough to wait for treatment.

Iovance, whose Philadelphia manufacturing facility can support production of therapies for more than 5,000 patients annually, has reduced manufacturing time to 22 days, and it is exploring a third generation TIL (LN-145) in Phase II trials that is manufactured in 16 days.

If that proves successful, the scope of eligible patients will broaden markedly, Singh and Mangal said.

However, significant industry-wide manufacturing challenges remain. These include a lack of standardized, scalable workflows and the prevalence of manual, labor-intensive processes. Further complicating the scaling up of production is the fact that manufacturing requires billions of therapeutic cells to reach clinical potency and that each patients’ cells are different.

As such, the next frontier will be developing automated, standardized, GMP-compliant workflows that reduce reliance on manual labor and slash time to production.

“The point-of-care model has been discussed quite a bit, where you have a small GMP environment near a hospital,” noted Mangal when asked about decentralized manufacturing. “But I don’t think we’re quite there yet. I don’t think anyone is doing it very successfully yet.”

Pricing And Commercialization

TIL therapies also face the same patient access issues as CAR-T. At $515,000 per patient, Amtagvi’s price tag “is costly, but it’s on par with the rest of the CAR-T landscape,” Mangal said, adding that “better patient access is certainly on the minds of everyone in the cell therapy field.”

“As more products come to market, companies will find ways to manufacture them more efficiently and lower the cost, which should drive patient access,” he said.

Contributing to the high cost of TIL therapies is the specialized nature of the treatment, beyond its unique manufacturing needs. TIL therapies are administered at certified centers with staff that have received specialized training and have inpatient monitoring capabilities. Currently, there are at least 50 authorized Amtagvi treatment centers in the US.

While the cost is high, Singh emphasized that like CAR-T, TIL is a one-time treatment.

“When you talk about the value proposition of these other really expensive therapies over a lifetime, a one-time therapy, I think there’s a lot of value there,” she said.

According to Mangal, Iovance has reported payers “being very receptive to the value proposition,” with insurers covering over 250 million lives having added Amtagvi to their medical policies as of early 2025. The treatment is also included as a preferred second-line or subsequent therapy in the National Comprehensive Cancer Network guidelines for melanoma treatment.

Looking forward, as more products enter the market, costs are likely to decrease. “With Iovance breaking ground on this particular therapy, other companies will be able to learn from their successes and challenges and be able to overcome them more easily,” Mangal noted.

Beyond Melanoma: The Future Of TIL Therapy

The initial focus of TIL therapy has been melanoma, due in large part to its high tumor mutational burden and antigen load. However, researchers are exploring the therapy’s potential in a range of other solid tumors, with a preponderance of studies in head and neck cancer, various gynecological malignancies and lung cancer.

“The lungs tend to be more immunogenic,” Singh explained, regarding the strong interest in applying TIL therapy to lung cancer. Indeed, she said, “We’ve seen immune checkpoint inhibitors have the most transformational impact on the treatment of lung cancer overall.”

She noted that over 45% of TIL-based therapies in development are being pursued by non-industry players, including academic institutions and hospitals. Along with the technology’s origins at the National Cancer Institute, this statistic reflects the importance of continued public funding in refining this important technology, and raises concerns about the Trump Administration’s cuts to research funding.

Genetic Engineering And Biomarkers

Additional advances being developed by Iovance and emerging competitors could increase the potency and convenience of TIL therapy. For example, Singh said a particularly interesting approach being tested by Iovance in Phase I trials is knocking out PD-1 on cells before they are put back into the patient.

Rather than administering combination therapy with a checkpoint inhibitor, this approach means “it’s actually making the inhibition before you administer the cells back to the patient.”

As for identifying patients that are most likely to benefit from TIL therapy, biomarker research is still exploratory. “We’re not at a place where we can identify predictive or prognostic biomarkers,” Singh noted, though she said early evidence suggests factors like HLA class I and II expression, neoantigen load and tumor mutational burden may help predict response.

The Road Ahead

As TIL manufacturers move forward in the clinic, Singh and Mangal will be watching for a growing number of solid tumor indications, increased access and expedited manufacturing, as well as the potential for TIL therapy to move to earlier lines of treatment, particularly in combination with checkpoint inhibitors. Indeed, Iovance is conducting a pivotal trial of Amtagvi with pembrolizumab for frontline advanced melanoma.

“That augmentation will be very interesting to see,” Singh said. “Hopefully that will bump up not only the response rate but also the durability.”

For a field that only recently achieved its first commercial approval, TIL therapy has rapidly established itself as a promising approach for some of oncology’s most challenging cancers, with significant room for further innovation and improvement in the years ahead.