Potent activity of soluble B7RP-1-Fc in therapy of murine tumors in syngeneic hosts |
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Authors: | Ara Gulshan Baher Angelo Storm Neal Horan Tom Baikalov Claudia Brisan Emil Camacho Reuben Moore Alison Goldman Hartt Kohno Tadahiko Cattley Russell C Van Gwyneth Gaida Kevin Zhang Ming Whoriskey John S Fong David Yoshinaga Steven K |
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Institution: | Department of Pharmacology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. |
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Abstract: | We have characterized a receptor:ligand pair, ICOS:B7RP-1, that is structurally and functionally related to CD28:B7.1/2. We reported previously that B7RP-1 costimulates T cell proliferation and immune responses (Yoshinaga et al., Nature 1999;402:827-32; Guo et al., J Immunol 2001;166:5578-84; Yoshinaga et al., Int Immunol 2000;12:1439-47). We report that B7RP-1-Fc causes rejection or growth inhibition of Meth A, SA-1 and EMT6 tumors in syngeneic mice. Established Meth A tumors were rejected effectively with a single dose of B7RP-1-Fc, however, the treatment was less effective on larger tumors. Mice that rejected Meth A tumors previously by Day 30, also rejected a subsequent Meth A challenge on Day 60, without additional B7RP-1-Fc treatment, indicating a long-lived memory response. Tumor cells believed to be less immunogenic, such as P815 and EL-4 cells, were less responsive to this treatment. The EL-4 responsiveness to the B7RP-1-Fc treatment was enhanced, however, by pre-treatment of the mice with cyclophosphamide. As expected, T cells appeared to be targeted by B7RP-1-Fc treatment. Thus, the administration of soluble B7RP-1-Fc may have therapeutic value in generating or enhancing anti-tumor activity in a clinical setting. |
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Keywords: | immunotherapy T‐lymphocyte costimulation ICOS B7RP‐1 tumor rejection |
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