Therapeutic vaccines present an attractive alternative to conventional treatments for cancer. However, tumors have evolved various immune evasion mechanisms to modulate innate, adaptive, and regulatory immunity for survival. Therefore, successful vaccine formulations may require a non-toxic immunomodulator or adjuvant that not only induces/stimulates innate and adaptive tumor-specific immune responses, but also overcomes immune evasion mechanisms.
Given the paramount role costimulation plays in modulating innate, adaptive, and regulatory immune responses, costimulatory ligands may serve as effective immunomodulating components of therapeutic cancer vaccines. Our laboratory has developed a novel technology designated as ProtEx that allows for the generation of recombinant costimulatory ligands with potent immunomodulatory activities and the display of these molecules on the cell surface in a rapid and efficient manner as a practical and safe alternative to gene therapy for immunomodulation.
Importantly, the costimulatory ligands not only function when displayed on tumor cells, but also as soluble proteins that can be used as immunomodulatory components of conventional vaccine formulations containing tumor-associated antigens (TAAs). We herein discuss the application of the ProtEx technology to the development of effective cell-based as well as cell-free conventional therapeutic cancer vaccines.