We have recently shown that the systemic administration of lymphokine activated killer cells (LAK cells) plus relatively low doses of recombinant
interleukin 2 (RIL-2) or the administration of high doses of RIL-2 alone can reduce the number of established pulmonary
metastases from the weakly immunogenic MCA-105
sarcoma in mice. We have now analyzed the therapeutic efficacy of these treatments on both weakly and nonimmunogenic
tumors of three distinct histological types in two different mouse strains. In all experiments, LAK cells were administered i.v. on days 3 and 6 and RIL-2 was injected i.p. from days 3 through 8 after
tumor induction. The MCA-101
sarcoma was completely nonimmunogenic as defined by its inability to successfully immunize C57BL/6 mice. Nevertheless, administration of LAK cells plus 7,500-10,000 units RIL-2 was highly effective in reducing the number of established 3-day pulmonary
metastases from this
sarcoma [at 7,500 units RIL-2, mean number of
metastases 37 +/- 11 (SE); P less than 0.05; at 100,000 units, 2 +/- 1; P less than 0.05] when compared to
Hanks' balanced salt solution treated control animals (116 +/- 9). Likewise, RIL-2 alone at doses of 20,000 units/injection or greater had significant antimetastatic effects (77 +/- 12; P less than 0.05). Established 3-day pulmonary
metastases from the MCA-38
adenocarcinoma in C57BL/6 mice and the M-3
melanoma in C3H mice were also susceptible to adoptive immunotherapy with LAK cells plus RIL-2 and with high dose RIL-2 alone. Treatment of mice with LAK cells alone or with low doses of RIL-2 alone (less than or equal to 20,000 units/injection) had little if any antitumor effects. LAK cells were tested for cytolytic activity in vitro against
tumor target cells of a variety of histological types; there was no discernible relationship between susceptibility to lysis by LAK cells in vitro and therapeutic efficacy in vivo. These findings have thus demonstrated that the successful
immunotherapy of established pulmonary
metastases with LAK cells plus RIL-2 or with high dose RIL-2 alone includes:
tumors that are immunogenic and nonimmunogenic;
tumors of distinct histological types such as
sarcoma,
adenocarcinoma, and
melanoma; and
tumors in at least two different mouse strains, C57BL/6 and C3H, and that there is little correlation between the in vitro lysability of
tumor cells by LAK effectors and the susceptibility of these same
tumors to successful
immunotherapy in vivo.