The universal character of the tumor-associated antigen survivin.
Survivin is expressed in most human neoplasms, but is absent in normal, differentiated tissues. Survivin is a bifunctional inhibitor of apoptosis protein that has been implicated in protection from apoptosis and regulation of mitosis. Several clinical trials targeting survivin with a collection of different approaches from small molecule antagonists to immunotherapy are currently under way. With regard to the latter, spontaneous anti-survivin T-cell reactivity has been described in cancer patients suffering from a huge range of cancers of different origin, e.g., breast and colon cancer, lymphoma, leukemia, and melanoma. Thus, survivin may serve as a universal target antigen for anticancer immunotherapy. Accordingly, down-regulation of survivin as a means of immune escape would severely inflict the survival capacity of tumor cells, which highlights this protein as a prime target candidate for therapeutic vaccinations against cancer. Data from several ongoing phase I/II trials targeting survivin for patients with advanced cancer will provide further information about this idea.
Andersen
Mads Hald
MH
Center for Cancer Immunotherapy, Department of Hematology, Herlev University Hospital, Herlev, Denmark. mahaan01@heh.regionh.dk
Svane
Inge Marie
IM
Becker
Jürgen C
JC
Straten
Per Thor
PT
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D014176:Protein Biosynthesis; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin