Jan 16 2008
The quest for an effective antitumor vaccine has received a boost from the results of work aimed at developing a nanoparticle that delivers tumor antigens to the immune system cells that trigger antibody production.
The results of this effort, led by Shinsaku Nakagawa, Ph.D., and Naoki Okada, Ph.D., of Osaka University in Japan, were published in the journal Biochemical and Biophysical Research Communications.
Vaccines are complex preparations of proteins and other materials designed to produce maximal immune response to those proteins. One factor that determines a vaccine’s potency is the ability of this mixture to trigger a recognition event between the protein antigen and immune system cells known as antigen-presenting cells (APCs). Using the biocompatible polymer poly(y-glutamic acid), the investigators were able to create self-assembling nanoparticles that entrap proteins as they form. The resulting nanoparticles were relatively stable, releasing their protein content over the course of a month. The investigators also demonstrated that they could freeze-dry these nanoparticles and reconstitute them without altering the functionality of the entrapped protein, a desirable property for any vaccine vehicle designed for use outside of major medical centers.
To determine whether these nanoparticles would trigger a useful immune response, the investigators entrapped the protein ovalbumin in the nanoparticles and then immunized three sets of mice with a metastatic ovalbumin-producing mouse melanoma. One set of mice received the nanoparticle, and the other two were immunized with either ovalbumin or a saline solution. Immunization consisted of three injections over the course of 1 week. Eighteen days after the last injection, the investigators examined the lungs of the treated mice, finding that there were virtually no metastatic lesions in the lungs of the nanoparticle-immunized mice. In contrast, mice immunized with either ovalbumin or saline had large numbers of metastatic nodules in their lungs.
Further experiments showed that the nanoparticles were taken up efficiently by APCs. In addition, the nanoparticles were able to traffic out of endosomes and release their protein antigens into the cytoplasm of the APCs, boosting the immune response to the antigen.
This work is detailed in the paper “Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.” An abstract of this paper is available through PubMed.