Engineers Use Natural Protein as Nanoshuttle for Anti-Cancer Vaccines

Source: National Institutes of Health

Summary: Researchers developed a new technology that enables nanovaccines to bind to the albumin protein naturally present in the body and get delivered to the target site.

Nanovaccines that work to mount an immune response against a tumor basically consist of 2 components – the part that delivers the vaccine to the correct site, the lymph nodes, where immune system activation happens; and the part that activates the immune cells to expand and specifically target the tumor. Cancer-fighting nanovaccines have shown significant promise, but the clinical application has been hampered by complications in large-scale manufacturing, quality control, and safety. Biomedical engineers from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) developed a new technology that enables nanovaccines to bind to the albumin protein naturally present in the body. The albumin protein then delivers these nanocomplexes to the lymph nodes, resulting in potent immune activation against multiple tumor types in mouse cancer models. The study findings were published in the journal Nature Communications.

Albumin-binding vaccine

Schematic of self-assembly of the AlbiVax nanovaccine. The tumor-specific antigen and DNA segment were attached to Evans blue (purple arrows). Upon injection, albumin in the blood (green arrows) binds to the Evans blue and brings the complexes into the lymph system where the DNA and antigen interact with the immune cells (blue) in the lymph nodes. The interaction triggers a vigorous immune response against the target tumor. Credit: Zhu, et al

Several nanovaccines were engineered, each with a different antigen and to each antigen a small dye molecule called Evans blue is also added which further binds to albumin. The vaccine-EB complex was named AlbiVax (albumin-binding vaccine). The nanovaccine also included a small segment of DNA bound to the EB; the DNA is a “danger signal” to the immune system and so helps make the immune response more robust. The research team is particularly optimistic about the long-lasting immunity that they were able to induce with the AlbiVax system, as evidenced by continued robust anti-tumor activity for up to 6 months. The use of natural albumin as a universal vaccine shuttle is a significant step towards the application of cancer nanovaccine immunotherapy in humans.

Post-doctoral fellow Guizhi Zhu said, “Albumin is an interesting protein and it has been studied for over 40 years for drug delivery using different technologies. Compared with other albumin-binding technologies, our proprietary technology has been developed using clinically safe EB, making it very promising for eventual clinical translation. By simply synthesizing albumin-binding vaccines, our technology can be applied to virtually any molecular vaccine or molecular therapeutics.”

More Information: Guizhi Zhu et al, “Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy”, Nature Communications (2017).  DOI: 10.1038/s41467-017-02191-y

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