New glioma vaccine in pipeline

Newsdesk New glioma vaccine in pipeline

Adapted from images courtesy of L Liau

A bacterial vaccine that exploits epitope model to induce an immune response not been engineered to produce LCMV. spreading protects rats from intra- against tumour cells made to express This strongly suggests that the immune cerebral challenge with glioma cells, the viral antigen,” explained Liau. system had become primed against opening up new possibilities of treating Rats vaccinated with the engineered both LCMV and the unknown native brain tumours with immunotherapy. bacteria were challenged with subcu- tumour antigens. “After sc-challenge, Although multiple modalities are taneous (sc) or intracerebral (ic) inject- the animals develop enhanced cerebral used to treat gliomas, the most com- ions of the modified gliosarcoma cells. tumour immunity because of epitope mon type of brain tumour, prognosis is The team first found that the vaccine spreading,” explained Liau, “and unlike poor and has not improved much the CD8-positive dependent over the past 20 years. Immunoresponse seen against sc tumours, 9L tumour ic Inject 105 cfu iv therapy has not been successful the immunity built up against against brain tumours because the endogenous brain tumour antigens rLM central nervous system is an involves CD4-positive T cells as immunologically privileged site. well: tumour immunity in the brain 7 days later 9L tumour sc Researchers in California (USA), appears to be different to tumour Recombinant Listeria monocytogenes expressing however, may have found a way to immunity anywhere else.” LCMV nucleoprotein overcome this problem. This method of inducing Linda Liau and co-workers at immunity is interesting to wouldRats resistant to sc tumour the University of Los Angeles, be designers of brain tumour inoculation resistant to subsequent ic challenge engineered Listeria monocytogenes vaccines because it means they may cells (a bacterium that readily Preclinical tests of a new glioma vaccine. not have to identify tumourexpresses antigens that induce specific antigens to foster an CD8-positive cytotoxic lymphocytes) was able to defend against sc-challenge, immune response capable of preventto produce lymphocytic choriomenin- but not ic-challenge. However, when ing tumour growth. Alfredo Prieto, gitis virus nucleoprotein (LCMV) as a those animals that had successfully oncoimmunology researcher at the tumour pseudoantigen. Gliosarcoma beaten off the sc-attack were later ic- University of Alcalá, Spain, told TLO: cells were also engineered to express challenged, all showed total resistance. “If this is applicable in man, it could LCMV. “No uniformly expressed tumEven more encouraging, vaccinated open up exciting new ways of tackling our-specific antigen has been found in animals were able to prevent ic- these notoriously difficult tumours.” brain tumours, so we used this bacterial challenges with glioma cells that had Adrian Burton

Potential new marker for ovarian cancer progression A potential new marker for ovarian cancer is under investigation by a group of researchers from the University of South Florida, USA. The group, led by Papineni Rao, measured the circulating concentrations of atrial natriuretic peptide (ANP) in the plasma and ascitic fluid of women with epithelial ovarian cancer. They found a correlation between the concentrations of ANP and an N-terminal fragment of proANP [proANP-(1–30)]. In 14 women undergoing surgery for ovarian carcinoma, plasma ANP concentrations were significantly higher than those in normal, healthy women. Furthermore, ANP and proANP-(1-30) concentrations in plasma were significantly higher than those in ascites fluid. According to the investigators, this pilot study is the

THE LANCET Oncology Vol 3 June 2002

first to demonstrate a correlation between ANP and proANP-(1-30) in both plasma and ascites fluid in women with epithelial ovarian cancer. The results were presented in April, 2002 at the annual meeting of the American Physiological Society, New Orleans, LA, USA. More than 75% of patients with epithelial carcinoma of the ovary, present with retroperitoneal or intraabdominal metastases because “there are no effective screening methods for the diagnosis of ovarian cancer”, explains Rao. He proposes that cancer cells may synthesise and secrete both ANP and proANP-(1-30), as has been shown previously in cases of small-cell lung cancer. However, Rao believes that ANP cannot yet be confirmed as a marker for ovarian cancer. “Further

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investigation is necessary to address this question,” he added. An independent observer commented that there are “considerably larger differences in CA125 or inhibin levels between ovarian cancers and controls”, which suggests that ANP may not be as good as current markers. Several other groups are searching for more specific ovarian cancer markers. Jim Kim (Brigham and Women’s Hospital, MA, USA) and colleagues have found evidence linking osteopontin concentrations and ovarian cancer; and increased expression of the proto-oncogene c-Ets1 has been shown to correlate with malignant potential in epithelial ovarian cancer by researchers in Japan. Cathel Kerr

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