title: Recombinant DNA technology for melanoma immunotherapy: anti-Id DNA vaccines targeting high molecular weight melanoma-associated antigen.
abstract: Anti-idiotypic MK2-23 monoclonal antibody (anti-Id MK2-23 mAb), which mimics the high molecular weight melanoma-associated antigen (HMW-MAA), has been used to implement active immunotherapy against melanoma. However, due to safety and standardization issues, this approach never entered extensive clinical trials. In the present study, we investigated the usage of DNA vaccines as an alternative to MK2-23 mAb immunization. MK2-23 DNA plasmids coding for single chain (scFv) MK2-23 antibody were constructed via the insertion of variable heavy (V H) and light (V L) chains of MK2-23 into the pVAC-1mcs plasmids. Two alternative MK2-23 plasmids format V H/V L, and V L/V H were assembled. We demonstrate that both polypeptides expressed by scFv plasmids in vitro retained the ability to mimic HMW-MAA antigen, and to elicit specific anti-HMW-MAA humoral and cellular immunoresponses in immunized mice. Notably, MK2-23 scFv DNA vaccines impaired the onset and growth of transplantable B16 melanoma cells not engineered to express HMW-MAA. This pilot study suggests that optimized MK2-23 scFv DNA vaccines could potentially provide a safer and cost-effective alternative to anti-Id antibody immunization, for melanoma immunotherapy.
authors.affiliation: Laboratory of Tumor Immunology, Scientific Technological Area, Italian National Research Center on Aging (INRCA), Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Barucca
authors.forename: M
authors.initials: M
authors.lastname: Capitani
authors.forename: M
authors.initials: M
authors.lastname: Cesca
authors.forename: D
authors.initials: D
authors.lastname: Tomassoni
authors.forename: U
authors.initials: U
authors.lastname: Kazmi
authors.forename: F
authors.initials: F
authors.lastname: Concetti
authors.forename: L
authors.initials: L
authors.lastname: Vincenzetti
authors.forename: A
authors.initials: A
authors.lastname: Concetti
authors.forename: F M
authors.initials: FM
authors.lastname: Venanzi
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000378:metabolism*; D004274:DNA, Recombinant / Q000235:genetics* / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy / Q000191:economics / Q000379:methods; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D018716:Molecular Mimicry; D010865:Pilot Projects; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000627:therapeutic use; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D004274:DNA, Recombinant; D057127:Single-Chain Antibodies; D019444:Vaccines, DNA; D000099216:Chondroitin Sulfate Proteoglycan 4