In a study the scientists show that antibodies, which have been successful in treating certain types of cancers, can effectively reach elusive intracellular targets, delaying tumour growth and prolonging survival when combined with chemotherapy.
"The study provides proof-of-principle for a powerful new strategy that may greatly expand the arsenal of potential targets for cancer drug development and that could be broadly applicable to many different cancer types," said Doctor Hiroyoshi Nishikawa of Osaka University.
The introduction of antibodies against cancer represents one of the biggest successes of cancer therapy over the past 20 years. These treatments work by targeting markers on the surface of cancer cells, and include the blockbuster therapies Herceptin, which targets the HER2/neu marker on breast cancer cells, and Rituxan, which targets the CD20 marker on B cell lymphoma.
The majority of markers that can distinguish cancer cells from normal cells, however, are found exclusively inside cancer cells, where antibodies typically cannot access them. "Therapies that can successfully target cancer antigens found within cancer cells may be able to fight cancer without causing unwanted side effects due to collateral damage to healthy cells," said study Doctor Gerd Ritter of the Ludwig Institute for Cancer Research (LICR).
To assess whether antibody treatment against an intracellular antigen might be successful, the researchers used an antibody against the prototypic cancer antigen NY-ESO-1 and tested it in a model of colon cancer engineered to express NY-ESO-1 within its cancer cells. Alone, the antibody had no effect against the cancer. By using chemotherapy to release NY-ESO-1 from the cancer cells prior to the administration of the antibody, however, they were able to significantly delay cancer progression and prolong survival. The researchers then tested the strategy in another cancer model using a different type of chemotherapy and showed similar results, demonstrating that this approach could be applicable to different tumour types using various standard chemotherapies.
By monitoring the immune responses to these treatments, the researchers on the study found that the anti-tumour effect of the combination was dependent on CD8+, or killer, T cells. Rather than working to kill the cancer cells directly, the antibody worked by binding to the NY-ESO-1 antigen and facilitating its presentation to CD8+ T cells, which then exerted the anti-tumour effects. These findings not only have implications for how scientists understand the mechanisms of current antibody treatments for cancer, but they also shed light on a fundamental question in clinical cancer immunology, which asks how people develop spontaneous antibody and/or CD8+ T cell responses against NY-ESO-1.
MEDICA.de; Source: Ludwig Institute for Cancer Research