Synthetic carriers that can target immunomodulatory drugs or vaccines to lymphoid organs or tumors are of great interest for increasing the safety and potency of immunotherapies. Two strategies recently developed in our lab for lymphatic and tumor targeting of immunomodulators will be described: Lymph node targeting is achieved clinically is sentinel lymph node mapping in cancer patients, where small-molecule dyes are efficiently delivered to lymph nodes by binding to serum albumin. To mimic this process in vaccine delivery, we synthesized amphiphiles designed to non-covalently bind vaccine antigens and adjuvants to endogenous albumin. These “albumin-hitchhiking” amphiphiles were efficiently delivered to lymph nodes following injection, leading to as much as 30-fold amplified cellular immune responses and anti-tumor immunity. In a second approach, we have pursued the development of ways to target cyclic dinucleotides (CDNs), hydrophilic small molecule agonists of the STING transcription factor, to lymph nodes or tumors for cancer immunotherapy. We designed amphiphiles that non-covalently associate with CDNs via cooperative hydrogen bonding, enabling their incorporation into nanofibers or nanodiscs for localized or systemic delivery. This approach shows promise to increase the potency of CDNs in vivo while lowering systemic inflammatory side effects, through tissue-specific targeting.

Polymer-lipid amphiphiles as carriers for vaccine antigens and immunomodulators

254th National Meeting (2017)

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