Induction of antitumor activity and experimental expansion of human lung cancer-infiltrating lymphocytes.

In order to look for effector cells which are more efficient and less toxic than LAK cells induced from PBL for use in adoptive immunotherapy, we studied the antitumor activity and in vitro expansion of tumor infiltrating lymphocytes (TIL) from human lung cancers and compared their cytological properties with those of autologous PBL. The results showed: 1) Large numbers of TIL could be obtained from lung cancer tissue, approximately 1-5 x 10(8)/g tumor tissue, with an average TIL to tumor cell ratio of 2.3:1 (21 samples). 2) Fresh TIL were not cytotoxic against either NK-sensitive or -resistant tumor targets. After culturing for 6 to 8 d in the presence of rIL-2, TIL showed significant cytotoxicity and were able to kill autologous and allogeneic tumor targets and fresh solid tumor targets. 3) When maintained in the presence of rIL-2, TIL were able to continue proliferating and expanding for more than 2 mon, with expansion indices of 4-512. TIL stopped proliferating following the disappearance of autologous tumor cells in the culture. 4) Chronological studies revealed that the cytotoxicity appeared after 4 days in culture and reached a peak on the 14th day, and cultured TIL remained cytotoxic for at least 4 wk.