Combinational adenovirus-mediated gene therapy and dendritic cell vaccine in combating well-established tumors.
Recent developments in tumor immunology and biotechnology have made cancer gene therapy and immunotherapy feasible. The current efforts for cancer gene therapy mainly focus on using immunogenes, chemogenes and tumor suppressor genes. Central to all these therapies is the development of efficient vectors for gene therapy. By far, adenovirus (AdV)-mediated gene therapy is one of the most promising approaches, as has confirmed by studies relating to animal tumor models and clinical trials. Dendritic cells (DCs) are highly efficient, specialized antigen-presenting cells, and DC-based tumor vaccines are regarded as having much potential in cancer immunotherapy. Vaccination with DCs pulsed with tumor peptides, lysates, or RNA, or loaded with apoptotic/necrotic tumor cells, or engineered to express certain cytokines or chemokines could induce significant antitumor cytotoxic T lymphocyte (CTL) responses and antitumor immunity. Although both AdV-mediated gene therapy and DC vaccine can both stimulate antitumor immune responses, their therapeutic efficiency has been limited to generation of prophylactic antitumor immunity against re-challenge with the parental tumor cells or to growth inhibition of small tumors. However, this approach has been unsuccessful in combating well-established tumors in animal models. Therefore, a major strategic goal of current cancer immunotherapy has become the development of novel therapeutic strategies that can combat well-established tumors, thus resembling real clinical practice since a good proportion of cancer patients generally present with significant disease. In this paper, we review the recent progress in AdV-mediated cancer gene therapy and DC-based cancer vaccines, and discuss combined immunotherapy including gene therapy and DC vaccines. We underscore the fact that combined therapy may have some advantages in combating well-established tumors vis-a-vis either modality administered as a monotherapy.
Research Unit, Health Research Division, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada.
Dajing
D
Xia
Terence
T
Moyana
Jim
J
Xiang
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D016207:Cytokines / Q000008:administration & dosage; D043525:Cytosine Deaminase / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology*; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011355:Prodrugs / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013937:Thymidine Kinase / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D016207:Cytokines; D011355:Prodrugs; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D013937:Thymidine Kinase; D043525:Cytosine Deaminase