Immunotherapeutic Cell-Based Vaccine to Combat Metastatic Breast Cancer

Abstract

Abstract : No significant improvements tor treatment of metastatic breast cancer have been developed in the last 20 years and the prognosis for women with this disease remains poor. Progress in understanding the immune response, however, has led to renewed enthusiasm for immune-based anticancer therapies. Previously, we demonstrated that tumor cell-based vaccines expressing MHC class II and 37.1 (CD80) molecules reduced experimental (i.v.-induced) and established spontaneous metastatic disease, by activating tumor-specific CD4(+) T-lymphocytes. We now demonstrate, using the mouse 4T1 mammary carcinoma, that a novel immunotherapy consisting of the cytokine IL-12 and SEB superantigen combined with the previously described cell-based vaccine produces an even greater reduction in spontaneous metastatic disease and significant extension of mean survival time in two distinct immunotherapeutic regimens. The therapeutic effect is particularly noteworthy because: (1) spontaneous metastatic cancer by 4T1 progresses similarly in comparison to human metastatic mammary cancer, (2) our post-operative model demonstrates that early metastatic lesions are primarily responsible for morbidity, (3) the metastatic disease is extensive prior to initiation of immunotherapy in both regimens, and (4) multiple effector cell populations, including T and NK cells, and anti-angiostatic factors are likely to mediate the anti-tumor effect.