Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma
Tusé D (1), Ku N (2), Bendandi M (3), Becerra C (4), Collins R Jr (5), Langford N (2), Sancho SI (6), López-Díaz de Cerio A (6), Pastor F (7), Kandzia R (8), Thieme F (8), Jarczowski F (8), Krause D (8), Ma JK (9), Pandya S (9), Klimyuk V (8), Gleba Y (8), Butler-Ransohoff JE (10).
(1) DT/Consulting Group, 2695 13th Street, Sacramento, CA 95818, USA.
(2) DAVA Oncology LP, Two Lincoln Center, 5420 LBJ Freeway, Suite 410, Dallas, TX 75240, USA.
(3) Ross University School of Medicine, P.O. Box 266, Portsmouth, Dominica.
(4) Baylor University Medical Center, C. A. Sammons Cancer Center, 3535 Worth Street, Dallas, TX 75246, USA.
(5) University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
(6) Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain.
(7) CIMA, Universidad de Navarra, Avenida Pío XII 55, 31008 Pamplona, Spain.
(8) Icon Genetics GmbH, Weinbergweg 22, 06120 Halle, Germany.
(9) St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
(10) Bayer Pharma AG, Gebäude 402, Raum 106, 42113 Wuppertal, Germany.
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.
CITA DEL ARTÍCULO Biomed Res Int. 2015;2015:648143. doi: 10.1155/2015/648143. Epub 2015 Sep 6.