A new strategy to induce effective antitumour response in vitro and in vivo.
To induce Her2-specific cell immune response, we used xenogeneic antigen rat neu L2-S2 domains as the vaccine antigen. The antigenic protein was engineered as a chimeric protein with human IgG1 Fc region (neu-Fc). Neu-Fc could stimulate the cell proliferation in mixed lymphocyte reaction effectively. Simultaneous neu-Fc and IFN-gamma stimulation dramatically elevated IL-12 secretion and reduced IL-10 production in PBMC. To further augment the activating effects on Th1-type response, Bacille Calmette-Guerin (BCG) was utilized as a non-specific stimulus. Neu-Fc, IFN-gamma and BCG costimulation exhibited the most conspicuous effects on the reversal of the Th1-type inhibitory effects by MCF-7 cell supernatant compared with neu-Fc alone or IFN-gamma and BCG costimulation. The lytic activity of effector cells to Her2 overexpressing cells was greatly promoted by neu-Fc, IFN-gamma and BCG stimulation simultaneously. Neu-Fc led to considerable retardation in EMT6/Her2 tumour growth in Balb/c mice. IFN-gamma and BCG efficiently enhanced the antitumour activity. A large amount of inflammatory cells were found to be accumulated in the tumour tissues or surrounded tumours in mice treated with neu-Fc, IFN-gamma and BCG but no inflammatory cell infiltration was observed in control tumours, indicating that the strategy is potent enough to support the initiation and propagation of tumour-specific immune response in an established tumour and generate a proinflammatory environment.
Wang
M
M
Institute of Basic Medical Sciences, Beijing, China.
Xie
Z
Z
Shi
M
M
Lu
H
H
Yu
M
M
Hu
M
M
Lu
F
F
Ma
Y
Y
Shen
B
B
Guo
N
N
D000818:Animals; D015478:Antigens, Heterophile / Q000008:administration & dosage / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases; D011961:Receptors, Fc / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D015478:Antigens, Heterophile; D001500:BCG Vaccine; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D016753:Interleukin-10; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C483804:Erbb2 protein, rat; C100688:Fc receptor, neonatal