Adoptive Cell Therapy for metastatic melanoma: A UK centre experience

Background
Adoptive cell therapy (ACT) with tumour infiltrating lymphocytes (TIL) has consistently demonstrated impressive clinical results in several international studies in the management of metastatic melanoma. We describe our experience as the only UK cancer centre currently providing TIL therapy.

Method
TIL are cultured from resected tumour samples as previously described. Infusion is preceded by non-myeloablative lymphodepleting chemotherapy (high dose cyclophosphamide and fludarabine) and followed by intravenous high dose interleukin 2 (HD-IL2).

Results
Twelve patients have been treated to date: Nine with cutaneous melanoma, two with ocular melanoma and one patient with mucosal melanoma. All patients had metastatic disease and were heavily pre-treated with a combination of targeted agents and immunotherapies (anti-CTLA4 and anti-PD1 antibodies). Over 75% of patients with cutaneous melanoma achieved an objective clinical response according to the response evaluation criteria in solid tumours, including two ongoing complete responses (33+ and 3+ months) and five partial responses. All other patients showed disease stabilisation with significant symptomatic improvement. One patient with ocular melanoma achieved a short lived partial response. All patients experienced anticipated toxicities associated with pre-conditioning chemotherapy and HD-IL2, which were short lived and manageable on the medical ward.

Conclusion
We show that at our centre lympho-depleting chemotherapy followed by transfer of autologous TIL and HD-IL2 is feasible and clinically effective, demonstrating tumour regression in over 75% of patients with metastatic cutaneous melanoma. Short lived responses were additionally seen in patients with ocular melanoma, where treatment options are limited, suggesting a potential role for TIL therapy in this group of patients also. Whilst treatment is safe, significant toxicities are attributable to HD-IL2 and further evaluation of TIL followed by low dose IL2 should be conducted to decrease treatment related complications and expand clinical participation in ACT.