Prostate cancer vaccine shows promise in early studies
MedWire News: Researchers from the UK and USA have created a novel vaccine that has "cured" well-established prostate tumors in mice, with no apparent side effects.
The vaccine consists of a complementary (c)DNA library created from healthy human prostate tissue - termed an altered self-antigen and epitope library (ASEL) - expressed in vesicular stomatitis virus (VSV). The VSV stimulates an immune response that then targets prostate tumor cells.
"The biggest challenge in immunology is developing antigens that can target the tumour without causing harm elsewhere," remarked study co-author Alan Melcher (University of Leeds, UK).
"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.
The researchers tested the efficacy of the ASEL vaccine against the mouse prostate tumor TC2. They found that intravenous ASEL generated a prostate-specific T-helper type 17 response.
Increasing the number of intravenous ASEL injections resulted in a more effective cure compared with intratumoral treatment. Specifically, nine intravenous injections of ASEL cured over 80% of mice with TC2 tumors, whereas nine intratumoral injections cured only 25%.
The team noted that there was no evidence of autoimmune prostatitis following the injections.
Suboptimal vaccination with three injections resulted in initial tumor regression with subsequent aggressive recurrence. However, tumor cells that escaped the initial immune pressure were readily treated by second-line virus-based immunotherapy that targeted the recurrent tumors.
"Nobody really knows how many antigens the immune system can really see on tumor cells," said study leader Richard Vile (Mayo Clinic, Rochester, Minnesota, USA).
"By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system. The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated."
"Virus-expressed cDNA libraries represent a novel paradigm for cancer treatment addressing many of the key issues that have undermined the efficacy of immuno- and virotherapy to date," conclude Vile and co-authors in the journal Nature Medicine.
They add that clinical trials could begin within 2 years.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Laura Dean