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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-08-2629.

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2002-08-2629v1
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Submitted August 29, 2002
Accepted December 13, 2002

The anti-CD22 ligand blocking antibody, HB22.7, has independent lymphomacidal properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts

Joseph M Tuscano*, Robert T O'Donnell, Laird A Miers, Linda A Kroger, David L Kukis, Kathleen R Lamborn, Thomas F Tedder, and Gerald L DeNardo

Department of Internal Medicine, University of California, Davis, Sacramento, CA, USA
Department of Hematolog and Oncology, Verterans Administration, Northern California Health Care System, Sacramento, CA, USA
Department of Immunology, Duke University, Durham, NC, USA
Brain Tumor Research Center, University of California, SanFrancisco, San Francisco, CA, USA

* Corresponding author; email: joseph.tuscano{at}ucdmc.ucdavis.edu.

CD22 is a membrane glycophosphoprotein found on nearly all normal B-lymphocytes and most B-cell lymphomas. Recent in vitro studies have identified several anti-CD22 monoclonal antibodies (mAbs) that block the interaction of CD22 with its ligand. One of these mAbs, HB22.7, has been shown to effectively induce apoptosis in several B-cell lymphoma cell lines. Lymphoma xenograft studies with Raji-tumored mice were used to assess the toxicity and efficacy of HB22.7 both alone and with combined modality immunotherapy (CMIT) with 90Y-DOTA-peptide-Lym-1 radioimmunotherapy (RIT). The effect of the sequence of these agents on the combined treatment was assessed by administering HB22.7 24 hours prior, simultaneously, or 24 hours after RIT. Within the groups treated with RIT alone or RIT and HB22.7 (CMIT), the reduction in tumor volume was the greatest when HB22.7 was administered simultaneously and 24 hours after RIT, and in the RIT treatment groups, this translated into the greatest overall response and survival, respectively. Overall survivals at the end of the 84 day CMIT trial were 67 and 50% in the groups treated with HB22.7 simultaneously and 24 hours after RIT, respectively. This compared favorably with the untreated and RIT alone groups which had 38 and 43% surviving at the end of the trial. Surprisingly, when compared to untreated controls, and all other treatment groups, the greatest cure rate and overall survival was observed in the group treated with HB22.7 alone with 47% cured and 76% surviving at the end of the 84 day trial. RIT clearance was not affected by treatment with HB22.7. When compared to RIT alone there was no significant additional hematologic (WBC, RBC, or platelet counts) toxicity when HB22.7 was added to RIT. Non-hematologic toxicity (assessed as change in body weight) was also unchanged when HB22.7 was added to RIT. Thus the anti-CD22 ligand blocking antibody, HB22.7, has independent lymphomacidal properties, and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts, without significant toxicity.


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