Virotherapy clinical trials for regional disease: in situ immune modulation using recombinant poxvirus vectors.
The ability of viruses to readily infect tumor cells both in vitro and in vivo has resulted in their study as antitumor agents through a variety of strategies. Replicating and conditionally replicating viruses and recombinant viruses encoding genes for toxins and/or prodrugs have been studied for their direct antitumor activity with promising results. However, to date, the lack of a targettable construct able to localize to all tumors following systemic administration has proven to be a major limitation in their use for metastatic disease. The ability of a variety of well-characterized viruses to serve as vectors for expression of tumor antigens and/or cytokines has also resulted in their study as immunotherapeutic agents. In this review, we discuss preclinical and clinical data that support the use of recombinant poxviruses as vectors for in situ tumor transfection with immune-enhancing cytokines and immune costimulatory antigens. We hypothesize that such an approach will ultimately lead to enhanced immune recognition of tumor and the development of an effective systemic antitumor immune response capable of eradicating primary and metastatic tumor foci.
Mastrangelo
Michael J
MJ
Department of Medicine, Division of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Lattime
Edmund C
EC
D002986:Clinical Trials as Topic; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000276:immunology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy / Q000821:virology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D011212:Poxviridae / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics
D016207:Cytokines; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor