Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck - A phase 1 study

Objective: To evaluate the feasibility and toxic effects of systemic adoptive T-cell immunotherapy in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN). Design: Nonrandomized phase 1 clinical trial. Setting: Academic tertiary care hospital. Patients: Between April 1, 1996, and September 30, 1998, 17 patients with confirmed recurrent and metastatic SCC of the upper aerodigestive tract were enrolled. Two patients did not receive T cells because of poor vaccine response. Fifteen patients were successfully treated with T-cell immunotherapy. Intervention: Patients were vaccinated on the thigh with irradiated autologous tumor cells admired with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by 3 additional daily injections of GM-CSF at the vaccination site. Eight to 10 days later, tumor cell vaccine-draining inguinal lymph nodes were resected, and lymph node lymphocytes were activated with staphylococcal enterotoxin A and expanded in interleukin 2 in vitro. Resulting cultured cells were infused into patients peripherally on an outpatient basis. Results: Toxic effects of infusion were limited to grade 2 reactions in 3 of 16 treatments. One patient required overnight hospitalization for fever and emesis. Median cell expansion was 37 times (range, 4-416 times), and median cell dose was 7.5 X 10(9) (range, 1.3 X 10(8) to 4.2 x 10(10)). Infused cells were predominantly CD3(+) (>97%), being a mixture of CD4(+) and CD8(+) cells. Three patients demonstrated stabilization of previously progressive disease. Two patients experienced favorable clinical courses after adoptive T-cell transfer, including 1 patient with no evidence of disease 4 years after surgical resection of a vertebral body metastasis. Conclusions: Adoptive immunotherapy is a technically feasible and safe treatment with low toxicity and may demonstrate therapeutic activity in patients with unresectable SCCHN.