Tobacco mosaic virus as a new carrier for tumor associated carbohydrate antigens.
Tumor-associated carbohydrate antigens (TACAs) are being actively studied as targets for antitumor vaccine development. One serious challenge was the low immunogenecity of these antigens. Herein, we report the results of using the tobacco mosaic virus (TMV) capsid as a promising carrier of a weakly immunogenic TACA, the monomeric Tn antigen. The copper(I) catalyzed azide-alkyne cycloaddition reaction was highly efficient in covalently linking Tn onto the TMV capsid without resorting to a large excess of the Tn antigen. The location of Tn attachment turned out to be important. Tn introduced at the N terminus of TMV was immunosilent, while that attached to tyrosine 139 elicited strong immune responses. Both Tn specific IgG and IgM antibodies were generated as determined by enzyme-linked immunosorbent assay and a glycan microarray screening study. The production of high titers of IgG antibodies suggested that the TMV platform contained the requisite epitopes for helper T cells and was able to induce antibody isotype switching. The antibodies exhibited strong reactivities toward Tn antigen displayed in its native environment, i.e., cancer cell surface, thus highlighting the potential of TMV as a promising TACA carrier.
Department of Chemistry, Chemistry Building, Room 426, 578 S. Shaw Lane, Michigan State University, East Lansing, MI 48824, USA.
Zhaojun
Z
Yin
Huong Giang
HG
Nguyen
Sudipa
S
Chowdhury
Philip
P
Bentley
Michael A
MA
Bruckman
Adeline
A
Miermont
Jeffrey C
JC
Gildersleeve
Qian
Q
Wang
Xuefei
X
Huang
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology; D001386:Azides / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology; D002213:Capsid / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D011487:Protein Conformation; D014027:Tobacco Mosaic Virus / Q000737:chemistry*
D015295:Antigens, Tumor-Associated, Carbohydrate; D001386:Azides; D019496:Cancer Vaccines; D004337:Drug Carriers; D007074:Immunoglobulin G; D003300:Copper