An experimental human vaccine that uses a “library of DNA” to stimulate the immune system to attack cancer cells without harming healthy cells, cured well-established prostate tumors in mice with no apparent side effects, wrote US and UK researchers in a study published this week in the journal Nature Medicine. The hope is that one day patients will receive such a vaccine without chemotherapy or radiotherapy and thus become tumor free while avoiding the toxic side effects of current treatments.
Lead author Dr Richard Vile, an immunologist at the Mayo Clinic in Rochester, Minnesota, US, told the press that:
“We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research.”
He said clinical trials could be under way within the next two years.
Immunotherapy or “vaccines” for cancer are not like conventional vaccines that aim to prevent disease: the aim is to wipe out already established disease or stop it spreading.
The holy grail of researchers in this new field is to stimulate the immune system to attack only the diseased part of an organ, without triggering a response that is so strong that it also attacks healthy tissue, as in an autoimmune disease.
The challenge is getting the immune system to recognize the unique fingerprint of antigens, molecular protein “tags” for that tissue and choose to respond only to the ones belonging to the diseased part of the tissue.
Other studies that have tried to vaccinate against prostate and other types of cancer tumors have not been very successful because the researchers have not been able to isolate a collection of tumor antigens that is sufficiently robust and diverse. The result is that the tumors mutate and gain a new foothold, in spite of the immune system’s response.
What is different and exciting about this study is that the researchers appear to have overcome this problem.
They assembled a complementary DNA (cDNA) library comprising gene fragments of healthy human prostate tissue.
They then inserted bits of cDNA into a swarm of vesicular stomatitis viruses (VSVs, these are known to stimulate an immune response) that were then cultured and injected into the bloodstream of mice with well-establised prostate tumors.
When the mice’s immune systems were exposed to the mutated viruses carrying bits of human prostate DNA, they recognized those antigens and mounted a strong immune response that attacked the prostate tumors in the mice. The tumors shrank and there were no traces of autoimmune diseases in the mice.
Co-author Alan Melcher, a professor and Cancer Research UK Senior Clinical Research Fellow at the University of Leeds in the UK, told the press that:
“The biggest challenge in immunology is developing antigens that can target the tumour without causing harm elsewhere.”
“By using DNA from the same part of the body as the tumour, inserted into a virus, we may be able to solve that problem,” he added.
Vile said nobody knows how many of the various antigens present on tumor cells the immune system can actually see.
“By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system,” he explained, adding that:
“The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated.”
He and his colleagues suggest that using viruses as vectors for the cDNA librares gives the immune system a more comprehensive picture of the cancerous invader and overcomes the problem of isolating antigens in tumor cells.
Funds from a private grant, Cancer Research UK, the National Institutes of Health, The Richard M. Schulze Family Foundation, and the Mayo Clinic helped pay for the study.
Professor Peter Johnson, chief clinician at Cancer Research UK, said the study was significant because it could really broaden the field of immunotherapy research. However, he was cautiously optimistic about whether the success seen in the mice can be replicated in humans:
“Although the vaccine didn’t trigger the immune system to overreact and cause serious side effects in mice, it will need to be further developed and tested in humans before we can tell whether this technique could one day be used to treat cancer patients,” said Johnson.
Timothy Kottke, Fiona Errington, Jose Pulido, Feorillo Galivo, Jill Thompson, Phonphimon Wongthida, Rosa Maria Diaz, Heung Chong, Elizabeth Ilett, John Chester, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher & Richard Vile.
Nature Medicine, Published online: 19 June 2011
DOI:10.1038/nm.2390
Sources: University of Leeds, Mayo Clinic.
Written by: Catharine Paddock, PhD