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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.

O'Donnell RT, Ma Y, McKnight HC, Pearson D, Tuscano JM - Cancer Immunol. Immunother. (2009)

Bottom Line: 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).Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, Cancer Center, Suite 3016, Sacramento, CA 95817, USA. robert.odonnell@ucdmc.ucdavis.edu

ABSTRACT
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.

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The effect of dosing schedule on tumor response rate. Groups of nine mice were treated with HB22.7 before Raji NHL tumors had become established. HB22.7 (1.4 mg) was administered on: Day 1, Day 1 and weekly for 6 weeks, Day 1 and every other week for 12 weeks, or were untreated. Mice were monitored for tumor volume (a), response rate (b) and survival (c)
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Fig3: The effect of dosing schedule on tumor response rate. Groups of nine mice were treated with HB22.7 before Raji NHL tumors had become established. HB22.7 (1.4 mg) was administered on: Day 1, Day 1 and weekly for 6 weeks, Day 1 and every other week for 12 weeks, or were untreated. Mice were monitored for tumor volume (a), response rate (b) and survival (c)

Mentions: The concept of treating relatively low-volume tumors was tested further. Mice were treated with HB22.7 (1.4 mg) 1 day after the implantation of the Raji cells; mice were followed for development of a tumor, its growth kinetics, and survival, Fig. 3. Early treatment (low tumor volume, non-established tumors) was at least as effective as the same dose and schedule of HB22.7 given to mice with small established tumors, Fig. 2. The CR rate for all mice treated with HB22.7 in this experiment was 9/27 (33%), similar to mice with small established tumors that were treated with HB22.7, see Fig. 2.Fig. 3


Dose, timing, schedule, and the choice of targeted epitope alter the efficacy of anti-CD22 immunotherapy in mice bearing human lymphoma xenografts.

O'Donnell RT, Ma Y, McKnight HC, Pearson D, Tuscano JM - Cancer Immunol. Immunother. (2009)

The effect of dosing schedule on tumor response rate. Groups of nine mice were treated with HB22.7 before Raji NHL tumors had become established. HB22.7 (1.4 mg) was administered on: Day 1, Day 1 and weekly for 6 weeks, Day 1 and every other week for 12 weeks, or were untreated. Mice were monitored for tumor volume (a), response rate (b) and survival (c)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749165&req=5

Fig3: The effect of dosing schedule on tumor response rate. Groups of nine mice were treated with HB22.7 before Raji NHL tumors had become established. HB22.7 (1.4 mg) was administered on: Day 1, Day 1 and weekly for 6 weeks, Day 1 and every other week for 12 weeks, or were untreated. Mice were monitored for tumor volume (a), response rate (b) and survival (c)
Mentions: The concept of treating relatively low-volume tumors was tested further. Mice were treated with HB22.7 (1.4 mg) 1 day after the implantation of the Raji cells; mice were followed for development of a tumor, its growth kinetics, and survival, Fig. 3. Early treatment (low tumor volume, non-established tumors) was at least as effective as the same dose and schedule of HB22.7 given to mice with small established tumors, Fig. 2. The CR rate for all mice treated with HB22.7 in this experiment was 9/27 (33%), similar to mice with small established tumors that were treated with HB22.7, see Fig. 2.Fig. 3

Bottom Line: 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).Various schedules of HB22.7 administration were tested; one dose every other week was more effective than more or less frequent dosing.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, Cancer Center, Suite 3016, Sacramento, CA 95817, USA. robert.odonnell@ucdmc.ucdavis.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus