2 research outputs found
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; <i>p</i> < 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