A new cancer treatment that uses a person’s own immune cells has been approved by the U.S. Food and Drug Administration (FDA) for treating the most dangerous type of skin cancer. Now this form of cellular therapy (tumor-infiltrating lymphocyte – or TIL therapy) is showing promise in advanced lung cancers through clinical trials underway at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).[1][2]

Giving immune system cancer-attacking power back
For a cancerous tumor to grow, it must overpower immune cells known as T cells. TIL therapy restores the immune system’s natural ability to fight cancer cells.

“T cells are major cancer-attacking immune cells. But we think they might not be robust enough to completely block and destroy the cancer; that’s why cancer grows. TIL therapy shifts the power back to the immune system to overcome the abnormal microenvironment inside a tumor that allows the cancer to grow unchecked by the immune system,” said Kai He, MD, PhD, a thoracic medical oncologist and physician-scientist with Pelotonia Institute for Immuno-Oncology at the OSUCCC – James.

What are TILs
Unlike some other cellular therapy techniques such as CAR T-cell therapy, TIL cells are not genetically re-engineered. Instead, specific immune-fighting T cells are extracted from the patient and grown from a few dozen immune cells to billions of cancer-blasting immune cells in a lab and then infused back into the patient.

This new army of healthy immune cells can then take hold in the body and target the cancer.

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Kai He, MD, PhD, discusses CT scan results with John Kosik at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. Kosick’s cancer is no longer detectable after receiving TIL therapy for advanced lung cancer.

How do TIL Therapy work
The process of getting a patient ready for TIL therapy starts with taking a biopsy, designed to remove and isolate the TILs from the tumor and grow them outside the patient to create an army of T-cells.  These T-calls are already primed to recognize and attack the cancer when given back to the patient because the were originally harvested from the patient’s cancer.

In the laboratory, the sample of the patient’s cancer is broken up in fragments.  These fragments are cultured in vitro in a growth medium containing recombinant interleukin-2 (rIL-2).

In this process, TILs proliferate while the tumor cells die off.  This results in billions of TILs being produced. After completing this process, the TILs are ready to be returned to the patient and deployed against the patients’s cancer.

To prep for this therapy, patients receive a one-time short course of chemotherapy to deplete the patients body of immunosuppressive immune cells, which to help to clear out unhealthy T-cells.  This also creates ‘space’ for the new TILs to take root. After this step has been completed, the patient is infused with the new, laboratory grown TILs and given IL-2, which stimulates the growth of TILs within the body.

One advantage of this therapy is that it is generally carried out only once.

First TIL therapy for advanced melanoma
In February, the company Iovance Biotherapeutics received the first US Food and Drug Administration (FDA) approval of a TIL therapy for the treatment of patuents diagnosed with unresectable or metastatic melanoma. The approval for lifileucel (Amtagvi®; Iovance Biotherapeutics) is a  milestone – it marks the first immune cell therapy approved for solid tumors made from TILs.

Working with Iovance, trials led in partnership by OSUCCC – James physician-scientists Richard Wu, MD, Joel Beane, MD, Kari Kendra, MD, PhD, Claire Verschraegen, MD and Dr. He provided essential clinical data that supported this approval. The OSUCCC – James Cellular Therapy Program is investigating TIL therapy for the treatment of other solid tumors, including lung and cervix cancers, as well as sarcoma and others. The team consists of scientists and physicians from various departments/divisions at OSU, including medical oncology, hematology, surgical oncology, pathology and others.

“Our goal is to give the most robust treatment early in the process to maximize benefit and increase chances of cancer control. It is very exciting to see TIL clinical trials producing complete responses in patients with stage 4 cancers with no evidence of disease afterward, especially in difficult-to-treat diseases like lung cancer and metastatic melanoma,” He said.

The team is working to produce novel TIL therapy products in-house at Ohio State for the treatment of lung and other solid tumors at the hospital’s 2,500-square-foot cell therapy manufacturing facility.

Highlights of prescribing information
Lifileucel (Amtagvi®; Iovance Biotherapeutics) [Prescribing Information]
Aldesleukin/rIL2 (Proleukin®; Iovance Biotherapeutics)[Prescribing Information]

Reference
[1] Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Graf Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. J Clin Oncol. 2021 Aug 20;39(24):2656-2666. doi: 10.1200/JCO.21.00612. Epub 2021 May 12. Erratum in: J Clin Oncol. 2021 Sep 10;39(26):2972. PMID: 33979178; PMCID: PMC8376325.
[2] Chesney J, Lewis KD, Kluger H, Hamid O, Whitman E, Thomas S, Wermke M, Cusnir M, Domingo-Musibay E, Phan GQ, Kirkwood JM, Hassel JC, Orloff M, Larkin J, Weber J, Furness AJS, Khushalani NI, Medina T, Egger ME, Graf Finckenstein F, Jagasia M, Hari P, Sulur G, Shi W, Wu X, Sarnaik A. Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. J Immunother Cancer. 2022 Dec;10(12):e005755. doi: 10.1136/jitc-2022-005755. PMID: 36600653; PMCID: PMC9748991.

Featured image: In the cell therapy lab at The Ohio State University Comprehensive Cancer Center— Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, scientists are able to manufacture a “living drug” to treat advanced cancer by isolating immune cells from a patient’s tumor, expanding them to billions of T cells and other immune cells that can be infused back to the patient. Photo courtesy: © 2024 OSUCCC – James. Used with permission,

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