High-scale expansion of melanoma-reactive TIL by a polyclonal stimulus: predictability and relation with disease advancement

The rationale of treating melanoma patients by infusion with tumor-infiltra ting leukocytes (TIL) is to perform an adoptive therapy through injection o f tumor-specific T cells. Nonetheless, methods currently used for ex vivo T IL expansion have not been evaluated for their efficacy to expand TAA-speci fic T cells. We have addressed this question here, using a culture method i n which high TIL growth was induced by a polyclonal T cell stimulus. Intrac ellular cytokine assays were performed to measure the proportion of T cells responding to autologous tumor cells among the lymphocytes from lymph node biopsies (TIL) of 26 patients with stage III melanoma. The data show that TIL from 18 of these patients contained detectable amounts of tumor-specifi c T cells before expansion. Although they decreased somewhat in percent abu ndance during expansion, they were still present afterwards, ranging from 0 .3 to 13.8%. Since a median number of 1.7 x 10(10) TIL was obtained from th ese patients (starting from 3.6 x 10(6) TIL), a total amount of tumor-react ive cytokine-secreting TIL of between 2.8 x 10(6) and 1.12 x 10(9) was obta ined in each case from 18 patients. The TIL populations from 8 patients did not contain tumor-reactive T cells: neither before expansion, nor after ex pansion. Lack of tumor-reactive TIL only occurs for patients bearing severa l tumor-invaded lymph nodes (40%), but not for those having a single invade d lymph node. Therefore, high numbers of tumor-reactive T cells can be prod uced, through a polyclonal TIL stimulation, from most early stage III melan oma patients but from only about half of the patients with a more dissemina ted disease. For this last group, the possibility of getting tumor-reactive TIL can be predicted by checking the presence of these cells before expans ion.