Clinical safety and Immunogenicity of tumor-targeted, plant-made id-klh conjugate vaccines for follicular lymphoma

Daniel Tusé, Nora Ku, Maurizio Bendandi, Carlos Becerra, Robert Collins, Nyla Langford, Susana Inogés Sancho, Ascensión López-Díaz De Cerio, Fernando Pastor, Romy Kandzia, Frank Thieme, Franziska Jarczowski, Dieter Krause, Julian K C Ma, Shan Pandya, Victor Klimyuk, Yuri Gleba, John E. Butler-Ransohoff

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Article number648143
JournalBioMed Research International
Volume2015
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Tusé, D., Ku, N., Bendandi, M., Becerra, C., Collins, R., Langford, N., Sancho, S. I., López-Díaz De Cerio, A., Pastor, F., Kandzia, R., Thieme, F., Jarczowski, F., Krause, D., Ma, J. K. C., Pandya, S., Klimyuk, V., Gleba, Y., & Butler-Ransohoff, J. E. (2015). Clinical safety and Immunogenicity of tumor-targeted, plant-made id-klh conjugate vaccines for follicular lymphoma. BioMed Research International, 2015, [648143]. https://doi.org/10.1155/2015/648143