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Cancer vaccines: the Antigenics approachCancer vaccines can be broadly classified into two categories: those that target unique antigens and those that target shared antigens.
Unique-antigen cancer vaccinesUnique antigens are antigens that occur only in cancer cells and do not exist in normal tissues. They arise from mutations that occur as the tumor cells grow uncontrollably. The vast majority of unique antigens are not only specific to cancer cells but also specific to each individual patient. As a result, the unique-antigen approach is potentially applicable to all cancer types, from solid tumors to hematological malignancies. Currently, the only way to produce a cancer vaccine using these unique antigens is by employing an autologous approach — meaning that the antigens are derived from the same individual they are used to treat. Preliminary indications of clinical benefit associated with autologous vaccine treatment have been observed in every indication tested — close to a dozen types of cancer. Autologous cancer vaccines in development include those utilizing whole cells, tumor lysates, RNA or heat shock proteins. Whole cells/lysates/RNAEarly attempts at autologous cancer vaccines involved whole cell preparations or lysates of a patient’s tumor, which were shown to be unsuccessful, as unpurified cellular contents send both stimulatory and suppressive immune signals. Although some success has been achieved using newer approaches, the complexity of the manufacturing process, issues with sterility, and difficulty in characterization of these complex autologous products make them less attractive from a commercial and regulatory standpoint. Heat shock proteinsAntigenics’ approach to cancer vaccines is based on heat shock proteins (HSPs), a ubiquitous family of proteins believed to play a role in the presentation of antigens on the cell surface to help the immune system recognize diseased cells. Among cancer vaccine approaches — autologous or otherwise — the HSP approach has achieved the highest degree of independent validation by researchers worldwide (see references), and has shown indications of clinical benefit in seven cancer types to date. The company’s HSP-based cancer vaccine Oncophage is designed to utilize the entire repertoire of unique antigens from an individual patient’s tumor to stimulate a strong tumor-specific immune response. Oncophage is a sterile protein preparation, manufactured using a simple and cost-effective process. Shared-antigen cancer vaccinesShared antigens are antigens that exist in normal tissues but are overexpressed in cancer cells. Because they are expressed in normal tissues, there is an increased tolerance for them, making shared antigens less likely to stimulate immune response. Moreover, if a cancer vaccine does overcome tolerance, autoimmunity can often be an unwelcome side effect. The majority of therapeutic cancer vaccines in development use a shared-antigen approach and differ only in the particular antigens used or the method used to attempt to overcome tolerance. The number of shared antigens necessary to target every cancer cell in any one patient and achieve clinical benefit across diverse patient populations is unknown.
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