Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin.
Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death.
De Lorenzo
C
C
Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, via Cinthia, Napoli 80126, Italy.
Troise
F
F
Cafaro
V
V
D'Alessio
G
G
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D012260:Ribonucleases / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002945:Cisplatin; D000939:Epitopes; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D012260:Ribonucleases; D000068878:Trastuzumab; C525747:Erb-hcAb; C518070:ERB-hRNase