HUMAN LUNG-TUMOR CELL SECRETION OF INTERLEUKIN-2 FOR PROTECTION AGAINST TUMOR ENGRAFTMENT

Background: Lung cancer continues to claim large numbers of human lives each year despite advances made in conventional therapies. The use of biologic response modifiers to modulate the immune system against human tumors is an alternate form of immunotherapy. Interleukin-2 (IL-2), or T-cell growth factor, is an important modulator of activated T cells. We show here that tumor cells transduced with human IL-2 cDNA provide protective immunity against engraftment of IL-2-secreting, as well as parental non-IL-2-secreting, tumor cells in vivo. Methods: In an attempt to increase the antigen-induced proliferation and cytotoxicity T cells within the vicinity of tumor antigen, we have transduced human lung tumor cell lines (generated from whole tumor specimens obtained fresh from the operating room) with a vector containing the IL-2 gene. Cell lines secreting 0.5-20 Cetus units/ml of IL-2 were generated. Control cell lines were similarly established using the same retroviral vector containing the gene for adenosine deaminase (ADA). The growth of tumor xenografts of the vector-modified cell lines was observed in severe combined immunodeficient (scid) mice. Results: Using C.B-17 scid mice, we have observed that the local secretion of IL-2 by these human lung tumor cell lines will prevent engraftment of that tumor into scid mice. The parental tumor as well as the tumor containing the ADA gene grow aggressively in the scid mouse. Growth arrest also correlated strongly with the amount of IL-2 secreted by the tumor cells. The local secretion of IL-2 by the transduced cell line will abrogate the tumorigenicity of the parental cell line as well as an allogeneic tumor. The inhibition of growth occurs only when the tumors are placed in close proximity to each other. After gamma irradiation, transduced tumor cells will continue to secrete IL-2. Conclusion: These results indicate that (a) human lung tumor cell lines can be transduced with IL-2-containing retroviral vectors; (b) local and sustained release of IL-2 will induce an antitumor response by the host against the IL-2-secreting as well as the control tumor cells; (c) secretion of IL-2 continues after the cells are irradiated. This study suggests that cytokine-secreting human lung tumors may be used in vaccination protocols for cancer patients.