Local Interleukin-2 Immunotherapy of Breast Cancer: Benefit and Risk in a Spontaneous Mouse Model

[摘要] Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pathological characteristics of the familial set of human breast cancer. Then we advanced a novel 3S–paradigm of anticancer research that helped to develop selection criteria and to estimate benefit/risk of local interleukin-2 (IL-2) effects in this spontaneous mouse model. In this paper, the efficacy of single and triple local IL-2 doses is compared using properly selected murine BLRB females based on our previously published data. Only BLRB females bearing spontaneous mammary tumors without subclinical period were used. The tumor growth rate and recipient survival of single and triple IL-2 applications were compared with corresponding parameter values of untreated control. Tumor growth rate was decreased in both experimental groups versus control parameter values. Single IL-2 application resulted in a significant prolongation of the average survival time while triple application caused acute tumor rejection in some females decreasing the survival time of the rest of the recipients. As a result, proper treatment protocol in accurately selected females allowed increasing the complete response rate to 14% in spontaneous mouse model of breast cancer. In conclusion, our approaches may demonstrate the principle methodology developing preselection procedure for breast cancer patients for local IL-2 therapy application.

[关键词] Breast cancer;Interleukin-2;3S–paradigm;Spontaneous mouse model;BLRB