AUGMENTATION OF THE LYMPHOKINE-ACTIVATED KILLER-CELL RESPONSE IN HEAD AND NECK-CANCER PATIENTS BY COMBINATION INTERLEUKIN-2 AND INTERFERON-ALPHA

The majority of patients with head and neck cancer present with advanced disease (stage III and IV), for which current chemotherapeutic regimens offer dismal results. Although known to have defects in their cell-mediated immunity, their poor performance status makes them unlikely candidates for aggressive immunotherapeutic protocols because of associated severe toxicities. This study evaluates the effect of subthreshold recombinant interferon-alpha (rIFN-alpha) and interleukin-2 (rIL-2) on the generation of lymphokine-activated killer (LAK) cells from the peripheral blood of patients with head and neck cancers. In vitro treatment of patients' lymphocytes consisted of incubation in 1,000 U/mL rIL-2, 100 U/mL, rIL-2, 100 U/mL rIFN-alpha, and 100 U/mL rIFN-alpha plus 100 U/mL rIL-2 for 4 to 5 days. Cytotoxicity was measured using a standard 4-hour chromium-51 (Cr-51)-release assay with Raji (B lymphoblastoid) tumor target cells. LAK activity was arbitrarily defined as greater than 20% cytolysis of Raji target cells. LAK activity was generated in a smaller percentage of the head and neck cancer patients by 1,000 U/mL rIL-2 compared with normal adult donors: 54% versus 100%, p < 0.05; IFN-alpha (100 U/mL) induced LAK activity in approximately 50% of the cancer patients. The addition of rIFN-alpha (100 U/mL) to rIL-2 (100 U/mL) resulted in LAK generation in a higher percentage of patients (83% versus 54%), as well as increased levels of cytotoxicity, p = 0.05. This combination also resulted in cytotoxicity levels equivalent to high-dose (1,000 rIL-2 U/mL). These in vitro data support a clinical trial to assess the therapeutic efficacy of combined low-dose rIL-2 and rIFN-alpha in vivo in head and neck cancer patients.