MedicalResearch.com Interview with:
Dr. Michael Lotze, MD
Chief Scientific Officer, Lion Biotechnologies
San Carlos, CA 94070
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Adoptive cell therapy (ACT) with Tumor-infiltrating Lymphocytes (TIL) has shown promise in mediating cancer regression which rely on activation in vivo compared to other immunotherapies that utilize genetically modified T-cells. In TIL therapy, autologous administration of TIL expanded outside the body elicits a highly individualized, specific and potent attack against the tumor. Clinical trials conducted at the National Cancer Institute evaluating TIL therapy for the treatment of metastatic melanoma reported overall response rates of up to 56%. The durable responses observed in these metastatic melanoma patients as well as other patients with cervical cancer, cholangiocarcinoma, and head and neck cancer signal the potential for broader application of TIL therapy to treat patients with other solid tumors, currently an area of substantial unmet clinical need. Lion’s study, recently presented at the Society for Immunotherapy of Cancer, sought to demonstrate the feasibility of culturing and expanding TIL isolated from non-melanoma tumors. We were successful in culturing TIL from tumors obtained from bladder, cervical, head and neck, lung and triple negative breast cancer.
MedicalResearch.com: What should readers take away from your report?
Response: Recurrent tumors are most often unresectable and nonresponsive to systemic cytotoxic and targeted treatments. TIL therapy is the only ACT to demonstrate encouraging results in solid tumors and have consistently shown similar response rates in treatment naïve and refractory metastatic melanoma patients who have failed other options including checkpoint inhibitors. To assess viability of TIL therapy in additional solid tumor indications for this study, TIL were harvested to assess cell count and viability followed by immunophenotyping. Phenotypic characterization of TIL from bladder, cervical and lung cancer were >60-70% CD8+ T cells whereas TILs from head and neck demonstrated variable distribution of CD8+ and CD4+ T cells. TIL propagated from TNBC were >80% CD4+ T cells. Regardless of the tumors, most cultures had <20% CD56+ NK cells. Based on this successful culturing of TIL, we can now explore the clinical feasibility of ACT for patients with other cancers.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We will investigate the clinical feasibility of ACT as a therapy for patients beyond metastatic melanoma. Efforts are currently focused on culturing TIL from smaller tumor specimens/biopsies and assessing means to promote the expansion of central and effector memory phenotypes and selecting for mutanome reactive TIL. Efforts to develop larger numbers and better TIL within the tumor prior to surgical excision are also being developed. Selection and enhanced retention of TIL following adoptive transfer strategies are also in development. Means to promote TIL growth over a shorter period of culture, allowing patients to be treated earlier with the ‘youngest’ TIL is a strategy we are also working on.
MedicalResearch.com: Is there anything else you would like to add?
Response: Other Lion data presented at SITC explored methods of process optimization including development of cryopreservation methodology and a more efficient assay to assess potency of TIL. The ultimate goal is to develop new and more effective ways to use TIL so that we can deliver personalized therapies to cancer patients with unmet medical needs.
Sethuraman et al. Successful Expansion and Characterization of Tumor Infiltrating Lymphocytes (TILs) from Non-melanoma Tumors.
2016 Society for Immunotherapy of Cancer Annual Meeting.
Poster Presentation Abstract #42. Presented November 12, 2016.
Disclosure: Study supported by:
Lion Biotechnologies, Inc.
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