A Personalized Tumor Vaccine Platform based on Bacterial Outer Membrane Vesicles via Plug-and-Display Technology
The recognition of tumor neoantigens by the immune system is a key event in the success of immunotherapy in oncology. However, only about 1% of these “foreign” neoantigens in cancer cells are spontaneously presented to the immune system. Therefore, using efficient vaccine vectors to display and present diverse tumor antigens is a major strategy in the development of effective anticancer therapeutics.
To address this challenge, a research team led by Profs. NIE Guangjun Nie and ZHAO Xiao from National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS), reported a flexible tumor vaccine platform. This work was recently published in Nature Communications.
In this work, scientists utilized genetic engineering and “Plug-and-Display” technology to construct the tumor vaccine platform based on outer membrane vesicles (OMVs) for rapid display of the target antigens (Figure 1). The protein catchers were fusing expressed with ClyA (a surface protein on OMVs). Meanwhile, various tumor antigens linked to the catchers’ tags can be rapidly and simultaneously displayed on the OMVs surface. The OMVs efficiently accumulate in draining lymph nodes by virtue of their small size (the “nano-size effect”) and biomimetic “foreigner” status. The amounts of pathogen associated molecular patterns (PAMPs) in OMVs derived from bacterial. Therefore, antigens loaded OMVs could realize the synergistic treatment of innate and adaptive immunity, and elicited dramatic antigen-specific immunity against a variety of tumors in vivo. More importantly, CC OMVs could stimulate the antigen-specific immune memory, and the antigen released from the vaccine-killed tumor cells also induce an antigen-spreading immunity.
In short, the research team established a “Plug-and-Display” OMVs tumor vaccine platform that can quickly display tumor antigens and achieve efficient lymph node delivery and immune stimulation. This “Plug-and-Display” design is more in line with the clinical needs of complex and changeable tumor antigens, which will greatly promote the development of individualized tumor vaccines.