Chemical synthesis and immunological evaluation of new generation multivalent anticancer vaccines based on a Tn...

Area of Science:

• Immunology
• Synthetic Chemistry
• Oncology

Background:

• Tumor-associated carbohydrate antigens (TACAs), like the Tn antigen, are crucial targets for synthetic anticancer vaccines.
• Developing effective vaccines that elicit potent immune responses against TACAs has been a significant challenge.

Purpose of the Study:

• To design, synthesize, and immunologically evaluate novel Tn-based vaccine candidates with multivalent antigen presentation.
• To compare the immunogenicity of native serine-linked (Tn-Ser) and oxime-linked (Tn-oxime) Tn antigen analogues.

Main Methods:

• Synthesis of high-valent vaccine prototypes (up to 16 copies) using late-stage convergent and divergent strategies with chemoselective click-type chemistry.
• Immunological evaluation in mice, assessing humoral and cellular immune responses against Tn antigen.

Main Results:

• The hexadecavalent Tn-oxime construct demonstrated robust, Tn-specific humoral and CD4+/CD8+ cellular immune responses.
• Generated antibodies successfully bound the Tn antigen on the surface of MCF7 cancer cells.
• The Tn-oxime analogue exhibited superior synthetic accessibility and immunological properties compared to Tn-Ser.

Conclusions:

• The fully synthetic, hexadecavalent Tn-oxime vaccine prototype is a promising candidate for further development.
• This approach offers a viable strategy for creating safe and effective synthetic anticancer vaccines targeting TACAs.