Importance, mechanisms and limitations of the distant bystander effect in cancer gene therapy of experimental liver tumors.
GCV-ablation of transplanted TK-positive liver tumors or the application of syngenic and allogenic HSV-TK/GCV oncolysates significantly reduced the size of synchronously growing untreated sister tumors in the liver. These TK-negative liver tumors constantly showed an increased infiltration by mononuclears (x4). The relative abundance of CD 4/8, NK and monocyte subtypes remained constant. The distant bystander effect was associated with a strong induction of GMCSF and IL-12 expression in the untreated TK-negative liver tumors. Analysis of the vbeta T-cell receptor profiles from TK-negative tumors did not point to clonal lymphocyte expansions. These results support the view of the 'distant bystander effect' as a predominantly local phenomenon, which is mediated by resident immune effectors rather than by MHC I restricted CD 3 positive lymphocytes.
Engelmann
Carsten
C
Laboratoire de Recherche Chirurgicale, Hôpital Cochin, 27 bd. du fg. St. Jacques, 75014 Paris, France. carsten.engelmann@charite.de
Heslan
Jean Marie
JM
Fabre
Monique
M
Lagarde
Jean Pierre
JP
Klatzmann
David
D
Panis
Yves
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D024201:Bystander Effect; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000628:therapy* / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D007124:Immunoenzyme Techniques; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000628:therapy* / Q000821:virology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics
D000998:Antiviral Agents; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D013937:Thymidine Kinase