Local adoptive immunotherapy employed on a selected population using IL2-activated immune cells (A-LAK cells) and IL2 resulted in complete growth inhibition of a human squamous cell carcinoma of the head and neck implanted three to seven days previously and growing in nude mice. Although the in vitro cytotoxicity of A-LAK cells against the carcinoma cells was not higher than that of the whole population (LAK cells), the in vivo antitumor efficacy was from 4 to 9 times higher for A-LAK cells, as confirmed by the total number of injected cells needed for a complete growth inhibition. In addition, local A-LAK cell administration was characterized by early peritumoral erythema and swelling, not observed during LAK-cell therapy, which disappeared at the end of therapy. Histology of the tumors, during and at the end of therapy, showed an initial granulocytic and plasma cellular infiltration followed by mononuclear infiltration of the stroma of the tumor. The tumors showed a terminal-like differentiation with an increase of the keratinic layer and decrease of basal epithelial cells. These effects were proportional to the number of A-LAK cells injected. With the highest number of A-LAK cells, a complete epithelial disorganization was observed and 4 weeks from therapy termination the tumors were reduced to keratinic areas surrounded by connective tissue. These observations suggest the possibility of a A-LAK cell-dependent process of accelerated tumor differentiation and keratinization leading to tumor regression in nude mice.
[Antitumor activity of adherent LAK cells (A-LAK) in a model of squamous carcinoma of the head and neck]
CAVALOT, Andrea Luigi;
1991-01-01
Abstract
Local adoptive immunotherapy employed on a selected population using IL2-activated immune cells (A-LAK cells) and IL2 resulted in complete growth inhibition of a human squamous cell carcinoma of the head and neck implanted three to seven days previously and growing in nude mice. Although the in vitro cytotoxicity of A-LAK cells against the carcinoma cells was not higher than that of the whole population (LAK cells), the in vivo antitumor efficacy was from 4 to 9 times higher for A-LAK cells, as confirmed by the total number of injected cells needed for a complete growth inhibition. In addition, local A-LAK cell administration was characterized by early peritumoral erythema and swelling, not observed during LAK-cell therapy, which disappeared at the end of therapy. Histology of the tumors, during and at the end of therapy, showed an initial granulocytic and plasma cellular infiltration followed by mononuclear infiltration of the stroma of the tumor. The tumors showed a terminal-like differentiation with an increase of the keratinic layer and decrease of basal epithelial cells. These effects were proportional to the number of A-LAK cells injected. With the highest number of A-LAK cells, a complete epithelial disorganization was observed and 4 weeks from therapy termination the tumors were reduced to keratinic areas surrounded by connective tissue. These observations suggest the possibility of a A-LAK cell-dependent process of accelerated tumor differentiation and keratinization leading to tumor regression in nude mice.
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