title: Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma.
abstract: We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11) displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE) related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies.
authors.affiliation: DT/Consulting Group, 2695 13th Street, Sacramento, CA 95818, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tusé
authors.affiliation: DAVA Oncology LP, Two Lincoln Center, 5420 LBJ Freeway, Suite 410, Dallas, TX 75240, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Ku
authors.affiliation: Ross University School of Medicine, P.O. Box 266, Portsmouth, Dominica.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bendandi
authors.affiliation: Baylor University Medical Center, C. A. Sammons Cancer Center, 3535 Worth Street, Dallas, TX 75246, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Becerra
authors.affiliation: University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Collins
authors.affiliation: DAVA Oncology LP, Two Lincoln Center, 5420 LBJ Freeway, Suite 410, Dallas, TX 75240, USA.
authors.forename: Nyla
authors.initials: N
authors.lastname: Langford
authors.affiliation: Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Susana Inogés
authors.initials: SI
authors.lastname: Sancho
authors.affiliation: Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Ascensión
authors.initials: A
authors.lastname: López-Díaz de Cerio
authors.affiliation: CIMA, Universidad de Navarra, Avenida Pío XII 55, 31008 Pamplona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pastor
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Kandzia
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Thieme
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Jarczowski
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Krause
authors.affiliation: St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Julian K-C
authors.initials: JK
authors.lastname: Ma
authors.affiliation: St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: Shan
authors.initials: S
authors.lastname: Pandya
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Klimyuk
authors.affiliation: Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Gleba
authors.affiliation: Bayer Pharma AG, Gebäude 402, Raum 106, 42113 Wuppertal, Germany.
authors.forename: John E
authors.initials: JE
authors.lastname: Butler-Ransohoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003710:Demography; D005260:Female; D006433:Hemocyanins / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008224:Lymphoma, Follicular / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011134:Polysaccharides / Q000276:immunology; D014026:Nicotiana / Q000378:metabolism*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D011134:Polysaccharides; D018074:Vaccines, Conjugate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin