Prostate cancer vaccine Prostvac successful in phase 1 trial with checkpoint inhibitor
An experimental therapeutic vaccine Prostvac extended survival of patients with advanced prostate cancer. Prostvac is manufactured by Denmark-based Bavarian Nordic.
The study enrolled 30 patients who had failed prior treatments. Prostvac was administered with increasing doses of ipilimumab, a checkpoint inhibitor that helps to boost immune responses. The experimental group showed an average survival of >30 months compared with <19 months in patients treated with chemotherapy. Among those who received the highest dose of ipilimumab, 20% were alive after 80 months.
"These data represent perhaps the most compelling survival benefit seen to date in this late-stage setting, and provide a strong rationale to continue to evaluate the combination of Prostvac and checkpoint inhibitors in follow-on clinical studies," Bavarian Nordic's CEO Paul Chaplin said in a press release.
Ipilimumab is approved for advanced melanoma but as a monotherapy it failed in trials with prostate cancer patients.
Majority of Americans support mandatory vaccination of children
Almost four in 5 Americans think that all children should be vaccinated unless there is a direct medical risk, according to an online survey conducted by the Reuters and Ipsos agencies that enrolled >6,000 US adults. Nearly half of the respondents opposed the idea that parents should be allowed to choose whether to vaccinate their children.
"The numbers are absolutely overwhelming in favor of vaccinations with a consistent minority in opposition," said Ipsos pollster Julia Clarke.
Only 13% of the respondents were against vaccination, with the highest opposition (17%) in the US. Far West, where most of the anti-vaccination movement is based.
The survey also found that older people tend to be more pro-vaccination and that >70% of Americans believe schools should be allowed to suspend unvaccinated children when there is a major disease outbreak.
Immunotherapy for advanced melanoma found to have long-term benefits
Checkpoint inhibitor ipilimumab has long-term benefits in patients with advanced melanoma, according to a follow-up study published in Journal of Clinical Oncology1. Administering ipilimumab together with the chemotherapy drug dacarbazine increased 5-year survival to 18% compared with 9% after chemotherapy only. In addition, low rates of serious adverse events were reported in a total sample of ∼500 patients.
Ipilimumab is marketed by Bristol-Myers-Squibb as Yervoy. It stimulates the immune system by blocking CTLA-4, which is an inhibitor of T-cell response. It has been approved for treatment of advanced melanoma and it is being tested on other cancer types as well.
1. Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD. Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial. J Clin Oncol. 2015; doi: 10.1200/JCO.2014.56.6018
Many US girls do not follow recommended HPV vaccination schedule
Almost half of teenage US girls did not receive HPV vaccine at a recommended age in 2012. Researchers from University of Texas analyzed National Immunization Survey of Teens 2008-12 data and examined how many girls of age <13 were immunized with available bivalent or quadrivalent vaccines. The recommended age for receiving the first of 3 injections is 11-12 years.
According to the results, reported in Vaccine 1, 56% of subjects complied with the recommendations in 2012, compared with 14% in 2008.
"Rates of HPV infection increase significantly every year for young people between 14 and 24, so vaccination at a young age is very important," said lead author Mahbubur Rahman. "It's important that parents and health care providers are aware of the importance of early HPV vaccination to ensure that girls receive this vaccination at the CDC's recommended age."
HPV is responsible for almost all cases of cervical cancer, and vaccination protects against 70% of HPV types. In addition, the quadrivalent vaccine protects against 90% of genital warts.
1. Rahman M, McGrath CJ, Hirth JM, Berenson AB. Age at HPV vaccine initiation and completion among US adolescent girls: Trend from 2008 to 2012. Vaccine 2015; 33:585-7
Preclinical and early clinical success for two Ebola vaccines
Two groups announced progress with Ebola vaccine development. A candidate developed by GSK-NIH collaboration showed an acceptable safety profile and immunogenicity in a Phase 1 trial. It is a recombinant viral-vectored vaccine with a single Ebola Zaire gene delivered by chimpanzee adenovirus.
The study was led by researchers at University of Oxford and published in New England Journal of Medicine 1. 60 healthy volunteers were divided into 3 groups, which received escalating doses of the vaccine. Immunogenicity was comparable across the groups and peaked at 14 days post-vaccination. The majority of adverse events were mild and lasted up to 2 days. Researchers are proceeding to a Phase 2 trial to be held in West Africa.
The second candidate from Novavax is a glycoprotein recombinant nanoparticle adjuvanted with Matrix‑M. It is highly immunogenic in non-human primates and advanced to a Phase 1 trial, which will enroll 230 healthy adults.
There are 2 more candidate vaccines being developed by Merck and Johnson & Johnson.
1. Rampling T, Ewer K, Bowyer G, Wright D, Imoukhuede EB, Payne R, Hartnell F, Gibani M, Bliss C, Minhinnick A, Wilkie M, Venkatraman N, Poulton I, Lella N, Roberts R, Sierra-Davidson K, Krähling V, Berrie E, Roman F, De Ryck I, Nicosia A, Sullivan NJ, Stanley DA, Ledgerwood JE, Schwartz RM, Siani L, Colloca S, Folgori A, Di Marco S, Cortese R, Becker S, Graham BS, Koup RA, Levine MM, Moorthy V, Pollard AJ, Draper SJ, Ballou WR, Lawrie A, Gilbert SC, Hill AV. A Monovalent Chimpanzee Adenovirus Ebola Vaccine - Preliminary Report. N Engl J Med 2015; doi: 10.1056/NEJMoa1411627
Two cancer immunotherapeutics received FDA's breakthrough designation
Based on positive clinical trial data, the US. Food and Drug Administration has granted Breakthrough Designation to 2 immunotherapeutics in order to speed up their development.
One is rindopepimut, produced by Celldex, which targets oncogene EGFRvIII (v3). It proved effective in patients with glioblastoma. "These patients have extremely limited treatment options, with only 3 new drugs approved in more than 20 years," Celldex' CEO Anthony Marucci said in a statement.
The other drug is Roche's MPDL3280A, PD-1-specific antibody that prevents tumors from inhibiting the immune system. The designation was granted for treatment of non-small cell lung cancer patients who failed chemotherapy.
Influenza vaccination can induce protection against avian strain H7N9
Antibodies against avian influenza H7N9 were isolated from individuals vaccinated against seasonal strains. Researchers purified 83 types of antibodies from 28 people, and found that 6 of them could broadly neutralize H7 viruses and 3 completely neutralized H7N9 and protected against virus challenge in mouse models. The results were published in Journal of Clinical Investigation 1.
The H7N9 influenza emerged in China 2 years ago and caused fears of global pandemics as mortality rate in infected humans reached 30%. "We have clear evidence that a normal immune response to flu vaccination offers protection against dangerous and highly unique strains of influenza such as H7N9," senior author Patrick Wilson of University of Chicago said in a press release. "We now need to develop ways of amplifying this response."
1. Henry Dunand CJ, Leon PE, Kaur K, Tan GS, Zheng NY, Andrews S, Huang M, Qu X, Huang Y, Salgado-Ferrer M, Ho IY, Taylor W, Hai R, Wrammert J, Ahmed R, García-Sastre A, Palese P, Krammer F, Wilson PC. Preexisting human antibodies neutralize recently emerged H7N9 influenza strains. J Clin Invest 2015; 125:1255-1268
DNA immunotherapy of ovarian cancer passes phase 1 trial
Celsion's GEN-1 therapy proved safe in patients with advanced platinum-resistant ovarian cancer. In a Phase 1b study, 16 people were given GEN-1 in combination with pegylated doxorubicin on a weekly basis. No toxicity or disease progression was observed. GEN-1 is a DNA therapy, wherein a vector expressing IL-12 is injected intraperitoneally into the tumor. IL-12, one of the most active cytokines, stimulates T cells and NK cells to proliferate and combat cancer cells.
Celsion researchers will proceed to a dose-escalation trial to determine therapeutically active doses. This study, which has been accepted by FDA, will enroll patients recently diagnosed with ovarian cancer, whose immune systems are stronger compared to patients with advanced tumor.
New transmission-blocking Malaria vaccine candidate produced in algae
A novel vaccine expressed in algae successfully protected mice from malaria. The candidate, a Pfs25 sexual-stage surface protein, is designed to prevent transmission of malaria from infected hosts to mosquitoes.
According to a study published in Infection and Immunity 1, the vaccine elicited a robust antibody response in mice. Moreover, when mosquitoes were fed blood from immunized mice 8 days later and their guts were analyzed, only 4% were positive for malaria, compared to 70% fed with blood from non-immunized mice.
"We are really excited to see that Pfs25 produced by algae can effectively prevent malaria parasites from developing within the mosquito," study co-author Stephen Mayfield of UCSD said in a statement. "With the low cost of algal production, this may be the only system that can make an economic malaria vaccine." In addition, expressing the protein in algae allows it to fold properly, which has been a major obstacle in other expression systems.
1. Patra KP, Li F, Carter D, Gregory JA, Baga S, Reed SG, Mayfield SP, Vinetz JM. Algae-produced malaria transmission-blocking vaccine candidate Pfs25 formulated with a human use-compatible potent adjuvant induces high affinity antibodies that block Plasmodium falciparum infection of mosquitoes. Infect Immun 2015; doi: 10.1128IAI.02980-14