Prostate cancer vaccine targeting telomerase
According to estimation from the International Agency for Research on Cancer (IARC) in men prostate cancer is the second most common cancer and ranks fifth as cause of death.
Telomerase is a reverse transcriptase enzyme that elongates telomeres by adding new DNA to the ends of chromosomes. In 85%of cancer telomerase allows tumour cells to escape senescence and to become immortal resulting in uncontrolled tumour growth. The reverse transcriptase subunit of telomerase (hTERT) plays a pivotal role in cancer development, being responsible of the immortality of tumour cells. hTERT is often overexpressed in cancer cells and its high expression is associated with poor prognosis.
The first-in-man immunotherapy clinical study using the second generation therapeutic hTERT cancer vaccine (UV1) has been recently published by W. Lilleby et al., from Oslo University Hospital-Radium Hospitalet This vaccine is directed against hTERT and has potential immunomodulating activity. Vaccination with the UV1 telomerase peptide might stimulate cytotoxic T-cells to recognize and kill telomerase-expressing cells (tumour cells).
The hypothesis of this study is that active vaccination against hTERT with UV1 telomerase peptide vaccine could provide a stronger immune response than the first-generation hTERT vaccine, and therefore provide clinical benefit in a larger proportion of patients. The key difference between first and second-generation hTERT vaccines is that UV1 consists of three hTERT peptides representing the epitopes most frequently recognised by long term cancer survivors, while first generation vaccine consists only of one peptide. The main objectives of the study are the assessment of safety and tolerability of the hTERT peptide therapeutic cancer vaccine UV1, the determination of immunological responses to UV1 and the selection of the biological dose of UV1 for further clinical studies.
This study aims to recruit 22 patients with newly diagnosed, histologically confirmed, prostate adenocarcinoma without visceral spread of the disease. The vaccine schedule consisted in a total of 13 vaccinations during a 26 weeks period.
The study results demonstrate a robust induction of hTERT-specific T cell in all three UV1 doses cohorts tested. The intermediate dose of 0.3 mg UV1 gave the highest frequency of immune responders. These are truly hopeful news for prostate cancer patients as the data suggest that the use of UV1 vaccine can enhance individual´s immune capabilities in men with prostate cancer providing a rationale for further clinical testing of the vaccine that could also demonstrate its clinical benefit.
Lots of questions still remaining and all very relevant to our favourite subject: telomere associated variables as cancer biomarkers: Will circulating tumour cells also be affected by UVI vaccination? Are telomere length and telomerase activity in prostate samples relevant biomarkers to predict response to treatment when targeting hTERT? Is telomerase activity in blood samples a useful way to triage prostate cancer patients? We hope to find the answers soon.