Targeting T cells against brain tumors with a bispecific ligand-antibody conjugate.
High-affinity receptors expressed on the surface of some tumors can be exploited by chemically conjugating the ligand for the receptor and an antibody against immune effector cells, thus redirecting their cytolytic potential against the tumor. Ovarian carcinomas and some brain tumors express the high-affinity folate receptor (FR). In this report, a transgenic mouse model that generates endogenously arising choroid plexus tumors was used to show that folate/anti-T-cell receptor antibody conjugates can direct infiltration of T cells into solid brain tumor masses. An engineered single-chain Fv form of the anti-T-cell receptor antibody KJ16 was conjugated with folate, to produce a bispecific agent that was substantially smaller than most previously characterized bispecific antibodies. Folate conjugation to the antibody increased T-cell infiltration into the tumors by 10- to 20-fold, and significantly prolonged survival of the mice.
Roy
E J
EJ
Department of Biochemistry, University of Illinois, Urbana 61801-3792, USA. e-roy@uiuc.edu
Cho
B K
BK
Rund
L A
LA
Patrick
T A
TA
Kranz
D M
DM
D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism; D016545:Choroid Plexus Neoplasms / Q000378:metabolism* / Q000628:therapy* / Q000648:ultrastructure; D005260:Female; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism / Q000494:pharmacology; D018796:Immunoconjugates / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000276:immunology*
D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm; D000952:Antigens, Polyomavirus Transforming; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D018796:Immunoconjugates; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D005492:Folic Acid