Cancer vaccines are one of the main means of cancer immunotherapy and prevention. Recently, Professor Liu Mi from the Department of Pharmacy at Suzhou University School of Pharmacy led a research team to publish a research paper online on Advanced Materials, reporting on the preparation method of a universal cancer vaccine. This method reassembles whole cell components of cancer cells or tumor tissue into nanoscale vaccines through PLGA nanoparticles for the prevention and immunotherapy of various types of cancer.
At present, the results obtained in the mouse model experiment show that the prepared nano vaccine can prevent 99.99% of lung cancer and 70% of melanoma. In addition, it can also effectively treat melanoma and triple negative breast cancer.
Professor Liu Mi introduced that the research team has applied for more than 10 international and domestic invention patents for the preparation method, related vaccine systems, and drug formulation systems of the nanovaccine.
▲ (a) Schematic diagram of recombining whole cell components of cancer cells or tumor tissue into nanovaccines; (b) Preparation plan for recombining whole cell components of cancer cells or tumor tissue into nanovaccines; (c) The mechanism diagram of cancer cell specific immune response induced by nano vaccines. (Image source: Reference [1])
Researchers have introduced that the limitations of traditional vaccine preparation techniques make it impossible to prepare cancer vaccines consisting of whole cell components of cancer cells and tumor tissue. Because many non water-soluble components in the whole cell fraction cannot be loaded into vaccine formulations for effective drug delivery. However, a large number of non water-soluble components (such as membrane proteins) contain many cancer specific and cancer-related mutations and neoantigens, which can provide important antigens for the immune system to recognize and eliminate cancer cells.
To address the aforementioned limitations, this study used 8M urea to solubilize non water-soluble components produced by cancer cells or tumor tissue lysis, and loaded both water-soluble and non water-soluble components into the nanovaccine. The whole cell components of cancer cells or tumor tissue were successfully reorganized into the nanovaccine (Figure a and b).
In order to increase the load of cancer antigens to a greater extent, whole cell components are simultaneously loaded inside and on the surface of the nanovaccine. Immune adjuvants are co loaded with whole cell components into nanovaccines to enhance their ability to activate antigen-specific T cells. Antigen presenting cells (APCs) prefer to engulf nanoscale substances, so nanovaccines are more easily engulfed by APCs and activate cancer cell specific immune responses (Figure c).
The results of cancer prevention experiments show that the nano vaccine prepared by this method can prevent 99.99% of mouse lung cancer and 70% of melanoma. The cancer therapeutic experiment found that nano vaccine can effectively treat melanoma and triple negative breast cancer in mice, and can make some mice (25%) recover. Simultaneously using anti-PD-1 antibodies can increase the cure rate of melanoma bearing mice treated with nanovaccines to 40%. In addition, metformin can further enhance the therapeutic effect of nanovaccines.
Researchers have also explored the mechanism by which this nanovaccine induces specific immune responses. They found that nanovaccines can efficiently induce tumor specific T cells and simultaneously activate adaptive and innate immune responses against tumor cells. Fluorescence multi target immunoassay analysis shows that nanovaccines promote the formation of tertiary lymphoid structures at the tumor site by increasing the content of immune cells, especially B cells, in the tumor microenvironment. Recent studies have shown that the formation of tertiary lymphoid structures at the tumor site is crucial for the effectiveness of cancer immunotherapy.
In addition, the nanovaccine increased the content of central memory T cells (Tcm), effector memory T cells (Tem), and tissue resident memory T cells (Trm) in mice. This creates a long-term immune memory in the mice that can recognize and kill cancer cells.
Professor Liu Mi pointed out that
