Potent activity of soluble B7RP-1-Fc in therapy of murine tumors in syngeneic hosts.
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.
Ara
Gulshan
G
Department of Pharmacology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
Baher
Angelo
A
Storm
Neal
N
Horan
Tom
T
Baikalov
Claudia
C
Brisan
Emil
E
Camacho
Reuben
R
Moore
Alison
A
Goldman
Hartt
H
Kohno
Tadahiko
T
Cattley
Russell C
RC
Van
Gwyneth
G
Gaida
Kevin
K
Zhang
Ming
M
Whoriskey
John S
JS
Fong
David
D
Yoshinaga
Steven K
SK
D000818:Animals; D015703:Antigens, CD / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018122:B7-1 Antigen / Q000627:therapeutic use*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D017252:CD3 Complex; C497965:Cd86 protein, mouse; D016207:Cytokines; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands; D008562:Membrane Glycoproteins; D003520:Cyclophosphamide