Jeffrey S. Weber, MD, PhD
After nearly 30 years of research, tumor-infiltrating lymphocyte (TIL) technology is being investigated as a means of producing personalized immunotherapy for patients with metastatic melanoma in a small clinical trial that may help open the door for broader application in other solid tumor types.
The form of adoptive cell therapy, which utilizes TILs from the patient’s tumor, represents an intriguing way of overcoming the immunosuppressive power of cancer, according to Jeffrey S. Weber, MD, PhD. The melanoma expert provided an overview of the technology and its potential benefit in a lecture for oncologists and oncology professionals presented by Targeted Oncology, a division of MJH Associates, the publisher of OncologyLive
, on February 19 in Miami Beach, Florida. Weber is the deputy director of the Laura and Isaac Perlmutter Cancer Center, co-director of its melanoma program, and head of Experimental Therapeutics at NYU Langone Medical Center.
Weber noted that TIL therapy employs a mechanism of action that is different from the checkpoint immunotherapeutic agents now approved in melanoma.
If approved, TIL therapy could be combined with PD-1 blockade agents as a first-line treatment or used in subsequent lines of therapy for patients with progressive disease, Weber indicated. “It’s yet another way of inducing remissions of long duration using an immunotherapeutic approach that’s different from ipilimumab and different from nivolumab or pembrolizumab,” said Weber. “It’s got its own toxicity, but you can fail this therapy and respond to ipilimumab or respond to nivolumab or pembrolizumab. You can fail nivolumab or pembrolizumab or ipilimumab and respond to this—they’re not cross-reactive.”
The mechanism of action for TILs is relatively straightforward, Weber said. Following resection, TILs are isolated from the tumor and are expanded to billions of cells in vitro. These potent TILs are then infused back into a patient. Ideally, TIL therapy is combined with preparative nonmyeloablative chemotherapy and posttransfer high-dose bolus interleukin-2 (IL-2), according to Weber.
Efficacy Evidence Building
Research into TILs began in the 1980s at the National Cancer Institute (NCI), where Weber was a fellow at the time. Today, TIL technology is being used at eight locations worldwide, including the NCI, The University of Texas MD Anderson Cancer Center, and the Moffitt Cancer Center in the United States. TIL therapy centers are being established at three additional locations around the world.
Weber noted that TIL technology looks promising so far—durable clinical responses have been observed in approximately 50% of patients with metastatic melanoma to date. More than 500 patients have been treated with autologous TILs plus IL-2 therapy during the past 10 years, he said. The approach has been pioneered in the laboratory of Steven A. Rosenberg, MD, PhD, a Giant of Cancer Care award winner who heads the NCI’s Tumor Immunology Section. In 2011, Rosenberg and colleagues reported durable responses among 93 patients with measurable metastatic melanoma.1 The patients were treated with cyclophosphamide and fludarabine alone or in conjunction with total body radiation of either 2 Gy or 12 Gy. A day after completing the regimen, patients began receiving infusions of TILs grown from previously resected melanoma lesions, along with high-dose IL-2.
After a median follow-up of 62 months, the objective response rate among all study participants was 56% (52 patients) including a 22% complete response rate (20 patients), most of which were ongoing for more than 3 years.1
Similarly, long-term responses have been evident among patients treated with TIL therapy at MD Anderson. The median overall survival (OS) among 73 patients was approximately 37 months from the time of TIL infusion, according to results referenced during the 2014 American Society of Clinical Oncology Annual Meeting.2
In an ongoing, unpublished study from Sarnaik et al at Moffitt, the TIL expansion process was successful in 93% (41/44) of patients, according to Weber. Of the 44 resected patients, 36 were treated with TIL technology. The median progression- free survival was 12 months with a median OS of 52 months. Eight of the 36 TIL technology- treated patients (22%) have durable ongoing responses from 26-54 months. Median follow-up on the trial is 17 months.