Optimized Nanoparticle Vaccines for Prostate Cancer

 

SDSU Co-Leader

Douglas Grotjahn, Ph.D.

UCSD Co-Leader

Boris R. Minev, M.D.

 

ABSTRACT

Among the body’s potential defenses are white blood cells called cytotoxic T lymphocytes (CTL). CTL can recognize and kill cancer cells, but only if they see complexes of protein fragments (peptides) attached to special molecules on the surface of the cancer cells. Several recent reports demonstrated the presence of anti-tumor CTL in blood from patients with brain tumors. It was also found that a protein called survivin exists in most prostate cancers. Importantly, little or no protein survivin was found in normal healthy tissues. We found recently several small pieces (peptides) derived from the protein survivin on the surface of the tumor cells. We confirmed that these small peptides could serve as targets for the anti-tumor CTL. Vaccine strategies aimed at the survivin protein may have important clinical applications because survivin is found at all malignant stages prostate cancer. We propose to design new vaccines for prostate cancer by using very small non-toxic particles, called nanoparticles. The nanoparticles allow encapsulation of the vaccines inside, protecting them against degradation.  Furthermore, the nanoparticle vaccine approach offers the possibility of providing tailor-made properties of the vaccine materials that may improve their function significantly. We will then use the new vaccines to “educate” in a test tube CTL from patients with prostate cancer so they recognize and kill the prostate cancer cells. We will determine whether the new vaccines can stimulate the anti-tumor CTL to kill specifically prostate cancer cells but not healthy cells. We will test the ability of the new nanoparticle-based vaccines to activate the anti-tumor CTL in rodents and to induce protective immunity against prostate cancer in rodents. The alternative to active immunization with the vaccines would be to generate the CTL in test tubes, expand them in number, then transfer them into the patient (adoptive transfer) to obtain direct kill to the prostate cancer cells. We will also explore this latter approach. The design of improved vaccines based on survivin-derived target peptides will undoubtedly contribute to the development of more efficient approaches for treatment of prostate cancer. These vaccines might be used directly to treat patients with prostate cancer. Therefore, the findings of this study will be used in clinical programs that will benefit many patients with prostate cancer.

Project Period: 9/1/2008 – 8/31/2012

Publications

Ma, W.; Chen, M.; Kaushal, S.; McElroy, M.; Zhang, Y.; Ozkan, C.; Bouvet, M.; Kruse, C.; Grotjahn, D.; Ichim, T.; Minev, B. “PLGA Nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses,” International J. Nanomed., 2012, 7, 1475-1487.

Presentations

Marly De Gracia, Andrea Rodriguez, Brigitte Martinez, Douglas Grotjahn, Boris Minev, “Preliminary Studies on Optimized Nanoparticle Vaccines for Prostate Cancer,” Student Research Symposium, University of California San Diego, San Diego, California. August 2010.

Andrea Rodriguez, Brigitte Martinez, Douglas Grotjahn, Boris Minev, “Preliminary Studies on Optimized Nanoparticle Vaccines for Prostate Cancer,” American Chemical Society 239th National Meeting, San Francisco, California, March 2010.

Andrea Rodriguez, Brigitte Martinez, Douglas Grotjahn, Boris Minev, “Preliminary Studies on Optimized Nanoparticle Vaccines for Prostate Cancer,” Student Research Symposium, San Diego State University, San Diego, California, March 2010.

Andrea Rodriguez, Brigitte Martinez, Douglas Grotjahn, Boris Minev, “Preliminary Studies on Optimized Nanoparticle Vaccines for Prostate Cancer,” 2009 ABRCMS National Conference, Phoenix, Arizona, November 2009.

Andrea Rodriguez, Brigitte Martinez, Douglas Grotjahn, Boris Minev, “Optimized Nanoparticle Vaccines for Prostate Cancer,” Minority Institution/Cancer Center partnership funded investigator workshop, Rockville, MD, September 2009.