Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: Safety and immunogenicity in a phase I clinical study
Plant-made vaccines have been the subject of intense interest because they can be produced economically in large scale without the use of animal-derived components. Plant-made therapeutic vaccines against challenging chronic diseases, such as cancer, have received little research attention, and no p...
Saved in:
| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 29; pp. 10131 - 10136 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
National Academy of Sciences
22-07-2008
National Acad Sciences |
| Subjects: | |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Plant-made vaccines have been the subject of intense interest because they can be produced economically in large scale without the use of animal-derived components. Plant-made therapeutic vaccines against challenging chronic diseases, such as cancer, have received little research attention, and no previous human clinical trials have been conducted in this vaccine category. We document the feasibility of using a plant viral expression system to produce personalized (patient-specific) recombinant idiotype vaccines against follicular B cell lymphoma and the results of administering these vaccines to lymphoma patients in a phase I safety and immunogenicity clinical trial. The system allowed rapid production and recovery of idiotypic single-chain antibodies (scFv) derived from each patient's tumor and immunization of patients with their own individual therapeutic antigen. Both low and high doses of vaccines, administered alone or co-administered with the adjuvant GM-CSF, were well tolerated with no serious adverse events. A majority (>70%) of the patients developed cellular or humoral immune responses, and 47% of the patients developed antigen-specific responses. Because 15 of 16 vaccines were glycosylated in plants, this study also shows that variation in patterns of antigen glycosylation do not impair the immunogenicity or affect the safety of the vaccines. Collectively, these findings support the conclusion that plant-produced idiotype vaccines are feasible to produce, safe to administer, and a viable option for idiotype-specific immune therapy in follicular lymphoma patients. |
|---|---|
| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: A.A.M., S.J.R., T.I.C., F.V., K.M.H., S.J.G., E.L.W., J.B., D.T., and R.L. designed research; S.R., S.J.R., T.I.C., D.K.C., F.V., and K.M.H. performed research; A.A.M., S.J.R., T.I.C., F.V., K.M.H., and R.B.H. contributed new reagents/analytic tools; A.A.M., S.R., D.K.C., S.J.G., E.L.W., J.N., J.B., and R.L. analyzed data; and A.A.M., S.R., S.J.R., T.I.C., D.T., and R.L. wrote the paper. Communicated by Charles J. Arntzen, Arizona State University, Tempe, AZ, May 2, 2008 |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.0803636105 |