Induction of tumor regression in experimental model of human head and neck cancer by human a‐lak cells and IL‐2

Abstract

In a nude mouse model of human squamous‐cell carcinoma of the head and neck (SCCHN), locoregional therapy with interleukin 2 and human lymphokine‐activated killer (LAK) cells resulted in a significant inhibition of growth of 3‐day established tumors. The same model was used for therapy of 7‐day established tumors with highly enriched populations of human adherent (A)‐LAK (CD3⁻ CD56⁺) cells and IL‐2. Peritumoral transfer of 10 × 10⁶ A‐LAK cells, whose in vitro cytotoxicity against a SCCHN cell line (PCl‐1) was not significantly different from that of LAK cells, resulted in complete regression of all 3‐day or 7‐day human SCCHN in nude mice. An initial inflammatory‐type reaction, which appeared within hours of the first peritumoral cell transfer, was accompanied by infiltration initially by granulocytes and plasma cells, and later by mononuclear cells into the tumor stroma. A‐LAK cells labelled with a fluorescent dye prior to injection appeared in the tumor stroma within 24 hr and were localized around or in the basal epithelial tumor layer by 48 hr. Histologic sections revealed an increasing epithelial disorganization and progressively decreasing basal epithelial layer, which were proportional to the increasing number of A‐LAK cells transferred. Within 4 weeks, the tumors were reduced to amorphous keratinic remnants surrounded by the connective tissue containing abundant mononuclear cells. Local administration of human A‐LAK cells and IL‐2 to SCCHN tumors growing in nude mice led to accelerated tumor differentiation, keratinization and regression.