Combined antiangiogenic and immune therapy may hold promise.(for breast cancer treatment)

2003 JAN 2 - (NewsRx.com & NewsRx.net) -- University of Pittsburgh researchers say a strategy that combines antiangiogenic and immune therapies may have potential to fight breast cancer.

"The therapeutic efficacy of combined antiangiogenic and immune therapy was tested against weakly immunogenic and highly metastatic 4T1 breast tumor using SU6668, an angiogenesis inhibitor and recombinant murine (rm) B7.2-IgG fusion protein, an immunostimulator. SU6668 inhibits the tyrosine kinase activity of three angiogenic receptors VEGFR2 (Flk-1/KDR), PDGFRbeta, and FGFR1, which play a crucial role in tumor-induced vascularization," said X.J. Huang and colleagues.

They explained that "rmB7.2-IgG is a fusion protein of the extracellular domain of B7.2, and the hinge and constant domains of murine IgG2a. Intermolecule disulfide linkages are maintained so that it forms a dimer.

"Our studies showed that three weekly immunizations of BALB/c mice bearing 0.5-0.8 cm 4T1 breast tumors with rmB7.2-IgG and irradiated 4T1 tumor cells (B7.2-IgG/TC) resulted in a significant inhibition of tumor growth and formation of pulmonary metastases," reported Huang's group. "T-cell depletion experiments revealed that both CD4+ and CD8+ T lymphocytes are required for stimulation of the antitumor and antimetastatic immune response by B7.2-IgG/TC.

"Treatment of mice with SU6668 substantially inhibited tumor vascularization but did not inhibit tumor infiltration by T lymphocytes or the T-cell response to rmB7.2-IgG therapy," the researchers said.

"On the contrary, tumors in mice immunized with B7.2-IgG/TC and treated with SU6668 had higher numbers of tumor infiltrating T cells than tumors of other groups. SU6668 treatments ...