TY - JOUR
T1 - Immunogenicity of dendritic-tumor fusion hybrids and their utility in cancer immunotherapy
AU - Shu, Suyu
AU - Zheng, Rongxiu
AU - Lee, Walter T.
AU - Cohen, Peter A.
PY - 2007
Y1 - 2007
N2 - Cancer immunotherapy using fusion hybrid cells generated from dendritic cells (DCs) and tumor cells may be more effective than other DC-based vaccines. DC-tumor fusion potentially confers not only the DCs' antigen-presenting functionality but also a continuing source of endogenous tumor antigens for major-histocompatibility-complex-restricted T-cell sensitization. In animal models, many investigators demonstrated that vaccination with fusion hybrids was protective against tumor challenge and therapeutic, resulting in the regression of established tumors. In clinical trials for patients with a variety of metastatic diseases, fusion hybrid vaccines were well tolerated, but the overall objective response rate was only 10.9%. Careful scrutiny of a large number of publications revealed that, in most cases, no definitive evidence of heterokaryonic fusion cell formation was found. Further corroboration of this conclusion comes from reports that fusion hybrids generated from autologous (syngeneic) and allogeneic DCs displayed equivalent immunological function and therapeutic effects in vitro and in vivo. This puzzling finding suggests that effective fusion immunotherapy depends on tumor antigen scavenging and presentation by antigen-presenting cells (APCs) of host origin and is in violation of the basic tenet of the principle of DC function. We believe that conclusions drawn from reported clinical trials have not properly evaluated the efficacy of the DC-tumor hybrid vaccine, and therefore, they neither confirm nor disclaim the potential benefits that may be derived from this form of immunotherapy.
AB - Cancer immunotherapy using fusion hybrid cells generated from dendritic cells (DCs) and tumor cells may be more effective than other DC-based vaccines. DC-tumor fusion potentially confers not only the DCs' antigen-presenting functionality but also a continuing source of endogenous tumor antigens for major-histocompatibility-complex-restricted T-cell sensitization. In animal models, many investigators demonstrated that vaccination with fusion hybrids was protective against tumor challenge and therapeutic, resulting in the regression of established tumors. In clinical trials for patients with a variety of metastatic diseases, fusion hybrid vaccines were well tolerated, but the overall objective response rate was only 10.9%. Careful scrutiny of a large number of publications revealed that, in most cases, no definitive evidence of heterokaryonic fusion cell formation was found. Further corroboration of this conclusion comes from reports that fusion hybrids generated from autologous (syngeneic) and allogeneic DCs displayed equivalent immunological function and therapeutic effects in vitro and in vivo. This puzzling finding suggests that effective fusion immunotherapy depends on tumor antigen scavenging and presentation by antigen-presenting cells (APCs) of host origin and is in violation of the basic tenet of the principle of DC function. We believe that conclusions drawn from reported clinical trials have not properly evaluated the efficacy of the DC-tumor hybrid vaccine, and therefore, they neither confirm nor disclaim the potential benefits that may be derived from this form of immunotherapy.
KW - Cancer immunotherapy
KW - Clinical trials
KW - Dendritic cells
KW - Dendritic-tumor fusion hybrids
KW - Electrofusion
KW - Tumor-associated antigens
UR - http://www.scopus.com/inward/record.url?scp=38049017405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38049017405&partnerID=8YFLogxK
U2 - 10.1615/critrevimmunol.v27.i5.50
DO - 10.1615/critrevimmunol.v27.i5.50
M3 - Review article
C2 - 18197808
AN - SCOPUS:38049017405
SN - 1040-8401
VL - 27
SP - 463
EP - 483
JO - Critical reviews in immunology
JF - Critical reviews in immunology
IS - 5
ER -