Researchers at the Pittsburgh Cancer Institute (PCI) announced lastweek that they are beginning clinical trials of a novel syntheticpeptide cancer vaccine following FDA approval of theirinvestigational new drug application on Dec. 13.
According to Olivera Finn, director of PCI's immunology program, thevaccine differs from previous agents in that it directly provokes theresponse of killer T cells rather than stimulating antibodyproduction. This cell-mediated immunity, Finn said, is much moreeffective against cancer than the more common antibody-basedtherapeutics. In addition, she said the immune response created bythe vaccine is "more specific than we've previously seen with othercancer vaccines."
The agent is developed from an abnormal form of mucin found onthe surface of breast, colon and pancreatic cancer cells. Mucin is acomplex of proteins and sugars found on the surface of both healthyand cancerous cells. In the case of cancer cells, however, the mucin'ssugar molecules are incompletely formed, revealing a limb of aninner protein that is normally hidden. These abnormal mucins canthemselves evoke the response of killer T cells, but according to thePCI researchers, their effect is highly inefficient.
The vaccine consists of concentrated mucin peptides and an adjuvantto attract immune cells. The antigen-presenting cells that are thebasis of most vaccines rely on a major histocompatibility complex(MHC) not universal to all patients, so such therapeutics are onlyeffective on patients with the right MHC.
Finn told BioWorld, however, that the synthetic peptide vaccinepresents a repeated chain of antigens that do not depend on aparticular MHC; instead, they bind with T cells at several sites,creating greater stability. Theoretically, therefore, all patientsexposed to the vaccine should develop a killer T cell response.According to Finn, the agent greatly increases both the odds that theright immune cells will encounter the mucin protein and theefficiency of the whole process.
The PCI researchers will be evaluating the effect of the agent in 30patients with widespread, incurable breast, colon or pancreaticcancer. The vaccination will be given in a series of three doses, eachthree weeks apart. After nine weeks, X-rays and physicalexaminations will be used to assess shrinkage of tumors. Blood testsand biopsies will be used throughout the course of the study toevaluate anti-mucin immune response at the vaccination site. Thevaccine can be given on an outpatient basis, and according to MichaelLotze, co-director of PCI's Biological Therapeutics Program, is lessdangerous than surgery and less toxic than chemotherapy orradiation therapy. Clinicals began Dec. 22.
PCI has no current plans for out-licensing of the agent. Finnexplained that at its current stage, the costs of developing thevaccine are within PCI's budget and she does not contemplate a near-term need to out-license.
The institute is one of 26 comprehensive cancer centers designatedand funded by the National Cancer Institute.
-- Karl A. Thiel Special to BioWorld
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