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BioMed Research International
Volume 2015 (2015), Article ID 648143, 15 pages
http://dx.doi.org/10.1155/2015/648143
Clinical Study

Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

1DT/Consulting Group, 2695 13th Street, Sacramento, CA 95818, USA
2DAVA Oncology LP, Two Lincoln Center, 5420 LBJ Freeway, Suite 410, Dallas, TX 75240, USA
3Ross University School of Medicine, P.O. Box 266, Portsmouth, Dominica
4Baylor University Medical Center, C. A. Sammons Cancer Center, 3535 Worth Street, Dallas, TX 75246, USA
5University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
6Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain
7CIMA, Universidad de Navarra, Avenida Pío XII 55, 31008 Pamplona, Spain
8Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany
9St. George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK
10Bayer Pharma AG, Gebäude 402, Raum 106, 42113 Wuppertal, Germany

Received 6 February 2015; Revised 11 April 2015; Accepted 12 April 2015

Academic Editor: Haiqing Ma

Copyright © 2015 Daniel Tusé et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.