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Systemic Adoptive T-Cell Immunotherapy in Recurrent and Metastatic Carcinoma of the Head and Neck
A Phase 1 Study
Wyatt C. To, MD;
Benjamin G. Wood, MD;
John C. Krauss, MD;
Marshall Strome, MD, MS;
Ramon M. Esclamado, MD;
Pierre Lavertu, MD;
David Dasko, BS;
Julian A. Kim, MD;
Gregory E. Plautz, MD;
Ben E. Leff, MD;
Vanessa Smith, MD;
Kate Sandstrom-Wakeling, RN, BSN;
Suyu Shu, PhD
Arch Otolaryngol Head Neck Surg. 2000;126:1225-1231.
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 admixed 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 109 (range, 1.3 x 108 to 4.2 x 1010). 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.
From the Department of Otolaryngology and Communicative Disorders (Drs To, Wood, Strome, Esclamado, Leff, and Smith) and Center for Surgical Research (Drs Krauss, Kim, Plautz, and Shu, Mr Dasko, and Ms Sandstrom-Wakeling), Cleveland Clinic Foundation, and the Department of Otolaryngology–Head and Neck Surgery, Case Western Reserve University (Dr Lavertu), Cleveland, Ohio.
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