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 therapeutic lymphocytes in head and neck squamous cell carcinoma.

DESIGN

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, and anti-CD3 antibody, and interleukin-2 (IL-2). Immunotherapy of mice bearing lung metastases was carried out in various experiments with low-dose systemic IL-2 and activated DLN cells. Using a 4-hour radioactive chromium Cr 51 release assay, in vitro cytotoxicity of these cells also was examined.

RESULTS

Mice immunized with this tumor failed to reject the growth of a subsequent challenge with the tumor. Immunotherapy with low-dose systemic IL-2 resulted in a mean reduction of 79% in the number of lung metastases. Adoptive immunotherapy with activated DLN cells was effective in all experiments, with a mean reduction of 59% in the number of metastases in immunodeficient mice. However, DLN cells were not directly cytotoxic to the 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 immunotherapy. Low-dose systemic IL-2 was effective in reduction of established metastasis in this model. Activated DLN cells show reproducible in 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 benefit.