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Published on: June 19, 2018
Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent
Jing-Jing Du1, Chang-Wei Wang1, Wen-Bo Xu1
1Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, International Joint Research Center for Intelligent Bio-sensing Technology and Health, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, China.
Abstract:
Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses. The IgG antibody titers elicited by the self-adjuvanting three-in-one protein conjugates were significantly higher than those elicited by the vaccine mixed with TLR7 agonist (more than 15-fold) or other traditional adjuvants. Importantly, the potent immune responses against cancer cells suggest that this new vaccine construct is an effective strategy for the personalized antitumor immunotherapy.
Insights
This study introduces a novel three-in-one cancer vaccine combining an adjuvant and tumor antigen on a single protein. This innovative approach enhances immune responses against cancer cells, overcoming challenges in traditional cancer vaccine development.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Cancer vaccines often fail due to immune tolerance challenges.
- Adjuvants are crucial for vaccine efficacy but can cause toxicity.
- Tumor-associated antigens are key targets for cancer immunotherapy.
Purpose of the Study:
- To develop a novel "three-in-one" anticancer vaccine construct.
- To enhance immune responses by integrating adjuvant and antigen.
- To overcome limitations of traditional cancer vaccine formulations.
Main Methods:
- Covalent conjugation of a TLR7 agonist (adjuvant) and MUC1 (antigen) to BSA (carrier protein).
- Creation of self-adjuvanting protein conjugates for enhanced immune stimulation.
- Evaluation of humoral and cellular immune responses in preclinical models.
Main Results:
- The three-in-one vaccine significantly increased adjuvant stimulation and reduced systemic toxicities.
- It facilitated co-delivery of adjuvants and antigens, enhancing immune responses.
- IgG antibody titers were over 15-fold higher compared to traditional vaccine mixtures.
Conclusions:
- The novel self-adjuvanting vaccine construct effectively breaks immune tolerance.
- This approach shows potent antitumor immune responses, suggesting efficacy in personalized immunotherapy.
- The integrated adjuvant-protein-antigen strategy represents a promising advancement in cancer vaccine development.
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