GENERATION OF THERAPEUTIC T-CELLS FROM DRAINING LYMPH-NODES IN A MURINE MODEL OF HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Objectives: To study immunotherapy for advanced head and neck squamous cell carcinoma using AT-84, a spontaneously arising murine tumor. We examined the draining lymph nodes (DLNs) for generation of potential t herapeutic lymphocytes in head and neck squamous cell carcinoma. Desig n: Experimental randomized control trial. Intervention: Therapeutic T cells from DLNs were generated by the sequential activation of the in vivo-primed DLN cells with 2C11, an anti-CD3 antibody, and interleukin -2 (IL-2). Immunotherapy of mice bearing lung metastases was carried o ut in various experiments with low-dose systemic IL-2 and activated DL N cells. Using a 4-hour radioactive chromium Cr 51 release assay, in v itro cytotoxicity of these cells also was examined. Results: Mice immu nized with this tumor failed to reject the growth of a subsequent chal lenge with the tumor. Immunotherapy with low-dose systemic IL-2 result ed in a mean reduction of 79% in the number of lung metastases. Adopti ve immunotherapy with activated DLN cells was effective in all experim ents, with a mean reduction of 59% in the number of metastases in immu nodeficient mice. However, DLN cells were not directly cytotoxic to th e tumor cells in in vitro assays, unlike control lymphokine-activated killer cells. Conclusions: AT-84 is a nonimmunogenic tumor similar to many human malignant neoplasms, making this a suitable model for;immun otherapy. Low-dose systemic IL-2 was effective in reduction of establi shed metastasis in this model. Activated DLN cells show reproducible i n vivo therapeutic efficacy despite lack of in vitro cytotoxicity. Use of DLN cells as sources of therapeutic T cells in patients with head and neck squamous cell carcinoma deserves exploration because they are readily obtainable and because conventional treatment is of limited b enefit.