The University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC) continues its reputation for cutting-edge care using innovative approaches to diagnosing and treating all types of cancer, and the latest advances in eliminating solid tumor cells are being led by Professor of Medical Oncology Ranee Mehra, MD.

In a recent effort to expand chimeric antigen receptor (CAR) T-cell treatment options, physicians at the UMGCCC are investigating the effectiveness of tumor-infiltrating lymphocyte therapy (TIL) as a treatment option.

TIL are naturally occurring immune cells that are on constant surveillance to recognize, attack and kill cancer cells through tumor markers that are unique to each person. Clinical trials are underway investigating the safety and efficacy of TIL therapy as monotherapy, and as part of combination therapy in advanced solid tumor cancers including melanoma, non-small cell lung cancer and cervical cancer. 

Reproducing and Growing TILs

Because TILs are taken directly from a patient’s tumor, they may recognize many of the unique targets specifically expressed on the surface of those tumor cells. The TILs that are in or near a specific tumor already can mount a response to unique proteins expressed by those cells revolutionizing current therapeutic modalities for solid tumors. This ability of TILs to recognize and respond to multiple tumor proteins decreases the likelihood of tumor cells evading the immune response by altering the expression of a single tumor-specific protein. 

If too few TILs are present to kill the tumor cells, or to overcome the signals that the tumor releases to suppress the immune system, doctors can test the lymphocytes in the lab to identify those that best recognize the patient’s tumor cells and treat the selected TILs with substances that make them reproduce and grow quickly. TIL therapy may be long-lasting and, in some cases, the TILs will continue to patrol the patient’s body for several years after a single infusion.

TIL Trials and Therapies

Next-generation TIL therapies, including genetically modified TIL, are also advancing toward clinical trials. 

A patient’s naturally occurring TIL are collected from a portion of their own tumor and grown outside the body using a manufacturing process to produce TIL therapy. This individualized TIL therapy is a one-time treatment to return these cells back to the patient. Once inside the body, TIL therapy deploys billions of personalized, patient-specific TIL to recognize and target diverse cancer cells.

Post-Therapy Care

TIL cell therapy is given only once forgoing the need for ongoing care. With combination therapy, patients first receive an immune checkpoint inhibitor followed by the one-time treatment, then receive maintenance treatment with an immune checkpoint inhibitor. 

Care includes a hospital stay of a few days so that doctors can monitor for any effects or reactions, which may develop shortly after the infusion. While the chance of any side effect is low, they do occur and could include fever, chills and shortness of breath up to two weeks following  the infusion. Patients are also given a drug, such as IL-2, to help stimulate TIL activity in the body and to manage any minor side effects. 

The Future of TIL Therapy

GCC 19125 is a prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent therapy is being conducted at multiple locations throughout North America and Western Europe including UMGCCC. 

LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL for the treatment of patients with unresectable or metastatic melanoma, advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.