Preliminary data of a small clinical trial at the University of California San Francisco Medical Center (CA, USA) have given hope to patients with recurrent brain cancer.
Oncophage® (Antigenics Inc., NY, USA) is a personalized cancer vaccine made from the patients’ own tumors. This trial involves 12 patients who suffer from recurrent glioma, in which glial cells that surround nerve cells develop into tumors. The tumors have been removed surgically but regrow afterwards.
This is a Phase I/II study designed to assess the safety and preliminary efficacy of Oncophage glioma vaccine. Each patient receives at least four doses of the vaccine. The first group of six patients has developed good antitumor immune responses and has exceeded the historical threshold of 6.5 months survival after tumor regrowth. No vaccine-related adverse effects have been observed so far.
“Based on preliminary observation of patients in the first cohort, the tumor-specific immune response evoked by vaccination may be associated with clinical benefit in these patients with recurrent glioma, including progression-free survival and overall survival compared with historical controls. Further studies are certainly warranted to definitely determine the benefit [of the vaccine] in this patient population,” said Andrew Parsa, the trial’s principal investigator.
A large Phase II clinical trial of this vaccine has been planned for 2007. Other Oncophage vaccines against skin and kidney cancers are also in the pipeline.
Source: The University of California, San Francisco, CA, USA (www.ucsf.edu).
New HIV DNA-vaccine candidates pass a Phase I clinical trial
Two new DNA-based vaccines against HIV have recently proven safe and well tolerated in healthy adults. The first vaccine is a plasmid mixture expressing Env proteins of HIV-1 clades A, B and C and a fusion protein (Gag–Pol–Nef) of HIV-1 clade B. The second vaccine utilizes a recombinant adenovirus (rAd5) to deliver the above HIV antigens.
“DNA [vaccine] is simple and does not have the problem of antivector immunity. However, DNA may be less potent than vector-based gene-delivery strategies. Replication-defective rAd5 has the advantage of targeted, efficient gene delivery and high potency but may be susceptible to antivector immunity,” explained Barney Graham, the lead author of the clinical trial.
Both vaccines were safe and well tolerated in healthy adult volunteers, although high doses of the vector-based vaccine caused pain and fever in some cases. More than 90% of the vaccinees developed CD4 T-cell responses and, on average, 50% had a positive CD8 T-cell response.
Virus-specific CD8 T cells clear the virus-infected cells, while “HIV-specific CD4 T-cell response correlates with long-term nonprogression of HIV disease”. The next step is “to evaluate the combination of DNA-priming and rAd5-boosting. Combining these distinct gene-delivery vaccination approaches has the potential to induce a different quality of response to either approach by itself,” added Graham.
The findings have been published in the December issue of the Journal of Infectious Diseases.
Source: Graham BS, Koup RA, Roederer M et al. Phase I safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J. Infect. Dis. 194, 1650–1660 (2006).
Trivalent inactivated influenza vaccine is safe for young children
A trivalent inactivated influenza vaccine appears safe for children of 6–23 months of age, reveals a study in the October issue of the Journal of the American Medical Association.
The vaccine was indicated initially for adults and certain children with medical conditions, such as asthma, which put them at higher risk of contracting influenza. However, there has been increasing evidence that normal children of less than 2 years of age are also highly susceptible to influenza infections. Therefore, in the winter of 2004, the US CDC extended its recommendation of influenza vaccination to this age group.
Simon Hambidge of Kaiser Permanente Denver (CO, USA) and colleagues have followed 45,356 children of 6–23 months of age and assessed vaccine-associated risks based on the number of medical visits and illness severity during the ‘risk window’, that is, the 42-day period following vaccination. The data were compared with those of the ‘control windows’, that is, before vaccination and after the risk window.
The authors found no significant increase in the frequency of medical visits for any serious conditions between the risk and the control windows. “Our study, the largest safety study of trivalent inactivated influenza vaccine in children aged 6 to 23 moths, adds to prior evidence that influenza vaccine is safe in infants and young children,” concluded the authors. They also suggest that similar studies in children aged 3–5 are necessary.
Source: Hambidge SJ, Glanz JM, France EK et al. Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old. JAMA 296(16), 1990–1997 (2006).