TY - JOUR
T1 - Clinical safety and Immunogenicity of tumor-targeted, plant-made id-klh conjugate vaccines for follicular lymphoma
AU - Tusé, Daniel
AU - Ku, Nora
AU - Bendandi, Maurizio
AU - Becerra, Carlos
AU - Collins, Robert
AU - Langford, Nyla
AU - Sancho, Susana Inogés
AU - López-Díaz De Cerio, Ascensión
AU - Pastor, Fernando
AU - Kandzia, Romy
AU - Thieme, Frank
AU - Jarczowski, Franziska
AU - Krause, Dieter
AU - Ma, Julian K C
AU - Pandya, Shan
AU - Klimyuk, Victor
AU - Gleba, Yuri
AU - Butler-Ransohoff, John E.
N1 - Publisher Copyright:
© 2015 Daniel Tusé et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1155/2015/648143
DO - 10.1155/2015/648143
M3 - Article
C2 - 26425548
AN - SCOPUS:84942278930
SN - 2314-6133
VL - 2015
JO - BioMed Research International
JF - BioMed Research International
M1 - 648143
ER -