Antigenic targeting of the human mannose receptor induces tumor immunity.
Pattern recognition receptors are preferentially expressed on APCs allowing selective uptake of pathogens for the initiation of antimicrobial immunity. In particular, C-type lectin receptors, including the mannose receptor (MR), facilitate APC-mediated adsorptive endocytosis of microbial glyconjugates. We have investigated the potential of antigenic targeting to the MR as a means to induce Ag-specific humoral and cellular immunity. hMR transgenic (hMR Tg) mice were generated to allow specific targeting with the anti-hMR Ab, B11. We show that hMR targeting induced both humoral and cellular antigenic specific immunity. Immunization of hMR Tg mice with B11 mAbs induced potent humoral responses independent of adjuvant. Injection of hMR Tg mice with mouse anti-hMR Ab clone 19.2 elicited anti-Id-specific humoral immunity while non-Tg mice were unresponsive. B11-OVA fusion proteins (B11-OVA) were efficiently presented to OVA-specific CD4 and CD8 T cells in MR Tg, but not in non-Tg, mice. Effector differentiation of responding T cells in MR Tg mice was significantly enhanced with concomitant immunization with the TLR agonist, CpG. Administration of both CpG and B11-OVA to hMR Tg mice induced OVA-specific tumor immunity while WT mice remained unprotected. These studies support the clinical development of immunotherapeutic approaches in cancer using pattern recognition receptor targeting systems for the selective delivery of tumor Ags to APCs.
He
Li-Zhen
LZ
Celldex Therapeutics, Bloomsbury, NJ 08804, USA.
Crocker
Andrea
A
Lee
Janine
J
Mendoza-Ramirez
Jose
J
Wang
Xi-Tao
XT
Vitale
Laura A
LA
O'Neill
Thomas
T
Petromilli
Chris
C
Zhang
Hui-Fen
HF
Lopez
Joe
J
Rohrer
Dan
D
Keler
Tibor
T
Clynes
Raphael
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000941:Antigens; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D007335:Insulin-Like Growth Factor II