title: A novel modified vaccination technique produces IgG antibodies that cause complement-mediated lysis of multiple myeloma cells carrying CD38 antigen.
abstract: Objectives were to: 1) induce a lytic IgG antibody (ab) response (via the so called `third vaccination method') against CD38 antigen (ag) residing on the extra-cellular domain of multiple myeloma (MM) cells in recipient rabbits, by combining the CD38 ag with donor-derived anti-CD38 ag lytic IgG ab into an immune complex (IC); and 2) determine whether abs produced would cause complement-mediated lysis (in vitro) of human MM cells containing CD38 ag. The vaccine was created in a two-step process. First, ab (rabbit anti-CD38 ag IgG ab) was raised in donor rabbits by injections of low molecular weight soluble CD38 ag in Freund's complete adjuvant (FCA) and aqueous solution. Second, transfer of pathogenic lytic IgG ab response into recipient rabbits was achieved by injections of ICs composed of CD38 ag and homologous anti-CD38 ag IgG ab. Consequently, recipient rabbits produced the same ab with the same specificity against the target ag as was present in the inoculum, namely agglutinating, precipitating and lytic (as demonstrated in vitro). In an in vitro study, in the presence of complement, donor and recipient rabbits' immune sera caused lysis of CD38 ag associated human MM cells. The most effective lytic ab response causing sera were those from donor rabbits injected with CD38 ag in FCA and those from rabbits injected with ICs, especially when they were administered in adjuvants. These results provided proof of concept that the third vaccination method has good potential as a stand-alone and efficacious method of controlling cancer.
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors.forename: Arpad Z
authors.initials: AZ
authors.lastname: Barabas
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Chad D
authors.initials: CD
authors.lastname: Cole
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Graeff
authors.affiliation: BioSante Pharmaceuticals, Inc., Doylestown, PA, USA.
authors.forename: Tulin
authors.initials: T
authors.lastname: Morcol
authors.affiliation: Department of Surgery, University of Calgary, Calgary, AB, Canada.
authors.forename: Rene
authors.initials: R
authors.lastname: Lafreniere
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000372:Agglutination Tests; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000936:Antigen-Antibody Complex / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G / Q000096:biosynthesis; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011817:Rabbits; D014611:Vaccination / Q000379:methods*
chemical_list: D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007106:Immune Sera; D007074:Immunoglobulin G; D003165:Complement System Proteins; D005620:Freund's Adjuvant; D051997:ADP-ribosyl Cyclase 1
keywords: Cancer; modified vaccination technique; prophylactic; therapeutic