Bioconjugate Chemistry
Bioconjugate Chemistry
5 years ago

Targeting CpG Adjuvant to Lymph Node via Dextran Conjugate Enhances Antitumor Immunotherapy

Targeting CpG Adjuvant to Lymph Node via Dextran Conjugate Enhances Antitumor Immunotherapy
Jingchao Xi, Myunggi An, Haipeng Liu, Weidong Zhang
Nucleic acid based adjuvants recognized by Toll-like receptors (TLR) are potent immune system stimulants that can augment the antitumor immune responses in an antigen-specific manner. However, their clinical uses as vaccine adjuvants are limited primarily due to lack of accumulation in the lymph nodes, the anatomic sites where the immune responses are initiated. Here, we showed that chemical conjugation of type B CpG DNA, a TLR9 agonist to dextran polymer dramatically enhanced CpG’s lymph node accumulation in mice. Dextran conjugation did not alter CpG ODN’s uptake, internalization, and bioactivity in vitro. Delivery of Dextran-CpG conjugate markedly increased the uptake by antigen presenting cells in the lymph nodes and enhanced CD8+ T cell responses primed by protein vaccines, leading to improved therapeutic antitumor immunity. Furthermore, immunization with Dextran-CpG mixed with necrotic whole tumor cells induced a protective antitumor response in a murine model, suggesting that this approach was not limited to molecularly defined antigens. This simple method might also be applicable for the delivery of many other nucleic acid based adjuvants in cancer vaccines.

Publisher URL: http://dx.doi.org/10.1021/acs.bioconjchem.7b00313

DOI: 10.1021/acs.bioconjchem.7b00313

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.