Search for HPV treatment vaccine heats up, researchers optimistic.

Will there ever be a vaccine to treat cervical cancer? If the number of candidate vaccines is any indication, the answer is yes. Researchers set their sights on a therapeutic vaccine for cervical cancer more than a decade ago when they learned that the disease is caused by a virus. But treatment vaccines targeted at the cancer culprit, human papillomavirus (HPV), have progressed slowly compared with HPV prevention vaccines, whose development began at the same time. Although two preventive vaccines are now speeding toward regulatory approval, no treatment vaccine has yet made it beyond a phase II trial. Recently, though, three companies have announced plans to follow up on phase II studies with randomized trials which, though not yet phase III, could be important for this fi eld. In April, Transgene Inc., MGI Pharma, and Stressgen Biopharmaceuticals Corp. all issued optimistic statements based on recent successes in early phase II trials focused on high-grade cervical dysplasia. “ We are extremely pleased by [our] results, ” said Transgene’s chief executive offi cer, Philippe Archinard, in a press conference. MGI Pharma and Stressgen have expressed similar confi dence in briefi ngs and Web postings in the last few months. The slow progress to this point has not been for lack of trying. Lab researchers have examined many diverse strategies to induce the T-cell response that could be essential to a successful immune system assault on cervical cancer cells. Concentrating on T cells — the other key weapon of the immune system, antibodies, will not work against cervical cancer cells — they have tried viral and bacterial vectors, fusion proteins, peptides, and DNA-based and dendritic cell – based vaccines, and more. Many have looked promising in the laboratory. “ Vaccine results in HPV-induced mouse tumors are absolutely excellent, ” said W. Martin Kast , Ph.D., an immunotherapy researcher at Norris Comprehensive Cancer Center in Los Angeles. “ It is beautiful in so many labs; you’re able to get rid of existing tumors. ” But time after time, results in the clinic have not lived up to expectations. Kast, who reviewed therapeutic HPV vaccine research at the annual meeting of the American Association of Cancer Research in April, counts 21 phase I or I/II trials that have been published, most with disappointing results. In late-stage cervical cancer, where new drugs are usually tested, there are still no positive results, he said. The one bright spot is that some therapeutic vaccines have shown signs of effectiveness against precancerous lesions, known as cervical intraepithelial neoplasia (CIN) 2 and CIN3. The three companies now planning large randomized trials have had their successes in this population. The disadvantage of focusing on this stage is that there is already a routine, fairly simple, outpatient treatment for CIN2 and 3 called loop electrosurgical excision procedure, or LEEP. Vaccine proponents point out, however, that about 10% of lesions recur after LEEP and that the procedure carries some risk of cervical damage. Besides, they say, patients would benefi t from a choice of treatments. LEEP, as Archinard pointed out, “ never comes with pleasure to the patients. ” Transgene, based in Strasbourg, France, is testing a therapeutic vaccine called TG4001. It uses the modifi ed vaccinia virus Ankara (MVA) to deliver two proteins, E6 and E7, which are the targets in virtually all the therapeutic vaccines developed to date. Unlike many other HPV proteins, E6 and E7 continue to be expressed in HPV-infected cells that have transformed into cancer cells. Transgene’s candidate vaccine is targeted at E6 and E7 specifi c to HPV16, the type of the virus most often found in cervical Search for HPV Treatment Vaccine Heats Up, Researchers Optimistic