Specifically Targeting the CD22 Receptor of Human B-cell Lymphomas with RNA Damaging Agents: A New Generation of Therapeutics

Miriam Hursey Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA

Dianne L. Newton SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA

Hans J. Hansen Immunomedics Inc., Morris Plains, NJ 07950, USA

Dale Ruby SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA

David M. Goldenberg Garden State Cancer Canter, Belleville, NJ 07109, USA

Susanna M. Rybak Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA

Abstract

Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA-damaging chemotherapeutics. A second generation construct with an improved recombinant cytotoxic RNAse is described. Targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin-containing immunoconjugates.

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Specifically Targeting the CD22 Receptor of Human B-cell Lymphomas with RNA Damaging Agents: A New Generation of Therapeutics

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Specifically Targeting the CD22 Receptor of Human B-cell Lymphomas with RNA Damaging Agents: A New Generation of Therapeutics

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