Boosting Immunity to Small Tumor-Associated Carbohydrates
with Bacteriophage Qβ Capsids
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Abstract
The development of an effective immunotherapy
is an attractive
strategy toward cancer treatment. Tumor associated carbohydrate antigens
(TACAs) are overexpressed on a variety of cancer cell surfaces, which
present tempting targets for anticancer vaccine development. However,
such carbohydrates are often poorly immunogenic. To overcome this
challenge, we show here that the display of a very weak TACA, the
monomeric Tn antigen, on bacteriophage Qβ virus-like particles
elicits powerful humoral responses to the carbohydrate. The effects
of adjuvants, antigen display pattern, and vaccine dose on the strength
and subclasses of antibody responses were established. The local density
of antigen rather than the total amount of antigen administered was
found to be crucial for induction of high Tn-specific IgG titers.
The ability to display antigens in an organized and high density manner
is a key advantage of virus-like particles such as Qβ as vaccine
carriers. Glycan microarray analysis showed that the antibodies generated
were highly selective toward Tn antigens. Furthermore, Qβ elicited
much higher levels of IgG antibodies than other types of virus-like
particles, and the IgG antibodies produced reacted strongly with the
native Tn antigens on human leukemia cells. Thus, Qβ presents
a highly attractive platform for the development of carbohydrate-based
anticancer vaccines