Thanks to the rapid development of nanotechnology, a researcher team led by Profs. NIE Guangjun, WU Yan and ZHAO Yuliang from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) recently designed personalized tumor vaccines based on bacterial cytoplasmic membranes and cell membranes from resected tumor tissue. This work was published in Science Translational Medicine.
Cancer vaccines are an effective anti-tumor therapeutic option that utilizes tumor antigens to stimulate the patients’ immune response and to specifically kill tumor cells. Postoperative recurrence and metastasis after surgery could be efficacy inhibited by the activated immune system. Therefore, it is the most important task for scientists and clinicians to find the best way to train the patient’s own immune system to find these tumor cells.
Meanwhile, it is a very attractive way to make a patient’s own anti-cancer vaccine using the surgically removed tumor tissues since it contains the personalized antigen spectrum of tumor cells. However, due to the small difference from the body’s own proteins, tumor antigens can be recognized as “self” by the patients’ own immune system. Then tumor antigens are more likely to induce antigen-specific tolerance rather than antitumor immunity.
Cancer immunotherapy faces the challenge how to educate the immune system to distinguish tumor components as “non-self”. Bacteria, most of time, are easily identified as invaders and cleaned by the immune system. Thus, researchers tried to use bacteria or their parts as adjuvants to enhance immunogenicity. However, nonspecific stimulation of the immune system by the bacteria or their parts may elicit severe side effects.
For example, lipopolysaccharides, a bad named cell wall compound of bacteria, may cause lethal cytokine storms. Therefore, it is critically important to develop powerful anti-cancer vaccines to educate the patients’ own immune systems to find the cancer cells, but not induce side effects.
In this work, the research team designed a hybrid membrane nanovaccine for personalized immunotherapy to overcome the challenges described above. The tumor membrane antigens and bacterial inner membrane are fused and displayed onto the surface of polymer nanoparticles. Introduction of cytoplasmic membranes of E coli, one of the most common bacteria in the human’s gut, into the hybrid membrane nanoparticle vaccines induced dendritic cell maturation, thus activating splenic T cells.
The hybrid membrane coated-nanoparticles represent a novel vaccine strategy that simultaneously delivers antigens and adjuvants to DCs to provoke robust innate and tumor-specific adaptive immune responses. In mouse tumor models, this strategy prevented tumor recurrence, with prolonged tumor-bearing animal survival and tumor-specific, long-term protection against tumor rechallenge.
In conclusion, the hybrid membrane-based antitumor immunity platform with intrinsic adjuvant properties offers a new opportunity for the development of individualized cancer vaccines for a broad range of solid tumors.
Prof. NIE’s group has long been engaged in anti-tumor immunotherapy with nanotechnology. They developed nano-inhibitors for targeting to two immune checkpoints through amphiphilic peptides (Nano Lett 2018; J Am Chem Soc 2020), natural nano-vesicles with chimeric immune checkpoint PD1 antibody (OMV-PD1) through genetic engineering technology (ACS Nano 2020), click chemistry based on active lymph node accumulation vaccine system (Adv Mater 2021), and a personalized vaccine platform for tumor antigen delivery using genetic engineering technology along with peptide molecular glue technology (Nat Commun 2021).
This project is supported by National Basic Research Program of China, the Strategic Priority Science and Technology Special Program of Chinese Academy of Sciences (Class B), the National Natural Science Foundation of China, and the Guangdong Provincial Key Research and Development Programs.