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Potent activity of soluble B7RP‐1‐Fc in therapy of murine tumors in syngeneic hosts
Author(s) -
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.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10831
Subject(s) - cyclophosphamide , meth , cancer research , immune system , receptor , downregulation and upregulation , biology , fc receptor , immunology , pharmacology , chemotherapy , medicine , chemistry , gene , biochemistry , acrylate , polymer , monomer , organic chemistry
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. © 2002 Wiley‐Liss, Inc.