Vaccines are routinely used in medicine to prevent infectious diseases such as chickenpox, mumps, as well as many others. We have previously discussed the complete eradication of smallpox from the world due to successful vaccination programs. We have also discussed the rise in the number of measles cases due to the fraudulent measles vaccine autism link. The use of vaccines in the treatment of cancers is much more limited. Recently, it was shown that a HPV vaccine was able to dramatically decrease the incidence of cervical cancer in Australian females. In addition, the use of the current hepatitis B vaccine can prevent some forms of liver cancer. These vaccines are classified as cancer preventive vaccines. The development of cancer treatment vaccines has not been as successful. The hope is that a cancer treatment vaccine will stimulate the body’s immune system and cause cytotoxic T-cells to attack the cancer cells. At this point in time, the U.S. Food and Drug Administration has approved only one cancer treatment vaccine for use in the treatment of patients. Sipuleucel-T (Provenge) is a cancer treatment vaccine that is approved for the treatment of metastatic prostate cancer. It is used in patients with metastatic prostate cancer that no longer respond to traditional hormone treatments, and allows these patients to live for an additional 4 months. The development of more cancer treatment vaccines has been very difficult. Recently, researchers lead by Dr. Richard Vile have reported online in the June 19, 2011 issue of Nature Medicine that they have developed a cancer treatment vaccine that successfully cured 80% of prostate cancer in a mouse model. Cancers express antigens on the surfaces of their cells, and previous attempts at developing a cancer treatment vaccine targeted these antigens. Previous attempts have failed because cancers mutate or change the antigens on their cell surfaces very quickly. The researchers that authored the Nature Medicine report used a novel technique to develop their cancer treatment vaccine, which overcomes this problem. Their vaccine was developed by inserting a human cDNA library from normal prostate cells into mutated vesicular stomatitis viruses. These viruses expressed a multitude of antigens from prostate tissue. The viruses were grown in culture and injected into mice that had established prostate cancer. After the researchers intravenously injected the mice with 9 inoculums of the vaccine, they were able to cure 80% of the prostate tumors in the mice. The success of this vaccine most likely stems from the use of the prostate cDNA library. By using a normal human prostate cDNA library, the researchers have given the immune system a more complete sampling of antigens that the cancer cells may express. This vaccine was also successful at stimulating the immune system to attack the prostate cancer cells while leaving other normal cell types unharmed. There was a theoretical concern that the vaccine would over stimulate the immune system and cause an autoimmune phenomenon but this was not observed. The researchers hope that the vaccine can be ready for human clinical trials in a few years. They also feel that because the vaccine does not target one particular cancer antigen, it can be more broadly applicable to the treatment of prostate cancer. Future studies will focus of the development of cancer treatment vaccines for other types of cancers, and the incorporation of this vaccine with traditional chemotherapy and radiation treatments. The authors wrote, “Therefore, virus-expressed cDNA libraries represent a novel paradigm by which the ability of highly mutable tumor cells to escape selective pressures in vivo can be exploited to therapeutic advantage”.
Dr. Alan Melcher talks about the research in this audio clip.
Timothy Kottke et al. “Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors” Nature Medicine published online 19 June 2011