2015
DOI: 10.1155/2015/561814
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A Humanized Anti-CD22-Onconase Antibody-Drug Conjugate Mediates Highly Potent Destruction of Targeted Tumor Cells

Abstract: Antibody-drug conjugates (ADCs) have evolved as a new class of potent cancer therapeutics. We here report on the development of ADCs with specificity for the B-cell lineage specific (surface) antigen CD22 being expressed in the majority of hematological malignancies. As targeting moiety a previously generated humanized anti-CD22 single-chain variable fragment (scFv) derivative from the monoclonal antibody RFB4 was reengineered into a humanized IgG1 antibody format (huRFB4). Onconase (ranpirnase), a clinically … Show more

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Cited by 21 publications
(12 citation statements)
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“…Previous studies have been conducted to conjugate ONC with antibodies targeted to tumor cells to increase its anti-tumor effect. After conjugation to the murine anti-CD22 IgG2a-mAb LL2 [31], ONC presented a promising payload for anti-CD22 immunoconjugates by combining high antitumor potency and low systemic toxicity [32]. In our studies, in order to improve the efficacy of ONC, we prepared a novel fusion protein by linking the TFn and rONC together.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies have been conducted to conjugate ONC with antibodies targeted to tumor cells to increase its anti-tumor effect. After conjugation to the murine anti-CD22 IgG2a-mAb LL2 [31], ONC presented a promising payload for anti-CD22 immunoconjugates by combining high antitumor potency and low systemic toxicity [32]. In our studies, in order to improve the efficacy of ONC, we prepared a novel fusion protein by linking the TFn and rONC together.…”
Section: Discussionmentioning
confidence: 99%
“…It was also evidently less toxicity. Weber et al performed and studied fusion anti-CD22 antibody with one and more molecules of onconase [64]. Cytotoxic effect in in vitro trial was the highest for conjugation with the number of three onconase.…”
Section: Targeted Therapeutic Rnases (Immunornases)mentioning
confidence: 99%
“…Fusion of ONC to a disease-specific antibody can direct its cytotoxicity to tumors with greater potency than the RNase in isolation. Newton et al [ 50 ], as well as Weber et al [ 51 ], have produced fusion proteins comprising of an anti-CD22 and ONC targeting B cell lymphomas. These showed significant in vitro and in vivo efficacy with as much as 104-fold increased toxicity in non-Hodgkin’s lymphoma cells in comparison to wild-type ranpirnase, with minimal side effects.…”
Section: Rnases Studied For Cytotoxicity and Anti-cancer Activitymentioning
confidence: 99%