Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine.
Development of an effective vaccine targeting tumor associated carbohydrate antigens (TACAs) is an appealing approach toward tumor immunotherapy. While much emphasis has been typically placed on generating high antibody titers against the immunizing antigen, the impact of immunogen design on the diversity of TACA-specific antibodies elicited has been overlooked. Herein, we report that the immunogen structure can significantly impact the breadth and the magnitude of humoral responses. Vaccine constructs that induced diverse TACA-binding antibodies provided much stronger recognition of a variety of Tn positive tumor cells. Optimization of the breadth of the antibody response led to a vaccine construct that demonstrated long lasting efficacy in a mouse tumor model. After challenged with the highly aggressive TA3Ha cells, mice immunized with the new construct exhibited a statistically significant improvement in survival relative to controls (0% vs 50% survival; p < 0.0001). Furthermore, the surviving mice developed long-term immunity against TA3Ha. Thus, both the magnitude and the breadth of antibody reactivity should be considered when designing TACA-based antitumor vaccines.
Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
Zhaojun
Z
Yin
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702, United States.
Sudipa
S
Chowdhury
School of Chemistry & Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
Craig
C
McKay
Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
Claire
C
Baniel
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702, United States.
W Shea
WS
Wright
Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
Philip
P
Bentley
School of Chemistry & Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
Katarzyna
K
Kaczanowska
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute , Frederick, Maryland 21702, United States.
Jeffrey C
JC
Gildersleeve
School of Chemistry & Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
M G
MG
Finn
Cellular and Molecular Immunology Laboratory, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine , Irvine, California 92697, United States.
Lbachir
L
BenMohamed
Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.
Xuefei
X
Huang
D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000145:classification*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL
D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines