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Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts
CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neop...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749165/ https://www.ncbi.nlm.nih.gov/pubmed/19437017 http://dx.doi.org/10.1007/s00262-009-0713-8 |
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author | O’Donnell, Robert T. Ma, Yunpeng McKnight, Hayes C. Pearson, David Tuscano, Joseph M. |
author_facet | O’Donnell, Robert T. Ma, Yunpeng McKnight, Hayes C. Pearson, David Tuscano, Joseph M. |
author_sort | O’Donnell, Robert T. |
collection | PubMed |
description | CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm(3) had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled-HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7. |
format | Text |
id | pubmed-2749165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-27491652009-09-23 Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts O’Donnell, Robert T. Ma, Yunpeng McKnight, Hayes C. Pearson, David Tuscano, Joseph M. Cancer Immunol Immunother Original Article CD22 is a cell-surface adhesion molecule on most B-cell NHL, so it is a promising target for immunotherapy. HB22.7 is an anti-CD22 mAb that binds the two NH(2)-terminal immunoglobulin domains and specifically blocks the interaction of CD22 with its ligand. CD22-blocking mAbs induce apoptosis in neoplastic B-cells and are functionally distinguishable from other anti-CD22 mAbs. This study assessed the optimal dose, route, schedule, and the targeted CD22 epitope. Raji NHL-bearing nude mice were studied. A non-blocking anti-CD22 mAb (HB22.27) was used as a control. HB22.27 had minimal effect, whereas HB22.7 improved survival and shrank tumors substantially. HB22.7 doses greater than 1.4 mg/week did not further increase efficacy (or toxicity). Tumors less than 200 mm(3) had a higher response rate than did larger tumors. Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing. Pharmacokinetic studies revealed that the half-life of HB22.7 was 28 days; this correlated with the time needed to re-populate cell-surface CD22 after treatment with HB22.7. Immuno-PET showed that NHL was rapidly and specifically targeted by copper-64-labeled-HB22.7. This study provided data as to an optimal dose, route, schedule and interval between doses of HB22.7. Springer-Verlag 2009-05-13 2009-12 /pmc/articles/PMC2749165/ /pubmed/19437017 http://dx.doi.org/10.1007/s00262-009-0713-8 Text en © The Author(s) 2009 |
spellingShingle | Original Article O’Donnell, Robert T. Ma, Yunpeng McKnight, Hayes C. Pearson, David Tuscano, Joseph M. Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title | Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title_full | Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title_fullStr | Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title_full_unstemmed | Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title_short | Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts |
title_sort | dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-cd22 immunotherapy in mice bearing human lymphoma xenografts |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749165/ https://www.ncbi.nlm.nih.gov/pubmed/19437017 http://dx.doi.org/10.1007/s00262-009-0713-8 |
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