Adoptive immunotherapy using tumor infiltrating lymphocytes in mice with spontaneous carclnoma.

Abstract

Adoptive immunotherapy was carried out using tumor infiltrating lymphocytes (TIL)cultured with rlL-2 after isolation from transplantable spontaneous squamous cell carcino-ma from inbred WHT/Ht lnice. Effector cells involved in antitumor reaction were investigated. TIL were collected at l×10⁵ cells/1gof tumor tissue. The viabnity amounted to more than 85% and the ratio of mixed tumor cells was less than 8%. By being cultured with rlL-2, TIL could be proliferated and maintained without tumor cells. A lymphocyte subsets were analyzed by FACScan. It was found that, fresh TIL were dominated by L3T4⁺ cells but a significant increase in Lyt-2⁺ cells was observed when TIL were cultured with rlL-2. The cytolytic activities of both cell lines were determined by means of ⁵¹ Cr release assay. Fresh TIL had no activity against syngeneic tumor cells, but cultured TIL had higher activity. These findings showed that the cytolytic activity was induced by rIL-2. Adoptive immunotherapy performed with cultured TIL produced no therapeutic effect in the group of TILalone, but had an inhibitory effect against tumor growth and a significant life-prolongation effect in the groups of TIL十rlL2 and CY十TIL十rlL-2. In conclusion, Lyt-2⁺ cells were presumed to play a main role in the cytolytic activity in TIL proliferated with rIL-2. TIL was suggested to be useful as a source of adoptive immunotherapy.