Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: a new generation of therapeutics.
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.
Hursey
Miriam
M
Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Newton
Dianne L
DL
Hansen
Hans J
HJ
Ruby
Dale
D
Goldenberg
David M
DM
Rybak
Susanna M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D015815:Cell Adhesion Molecules; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D037102:Lectins / Q000037:antagonists & inhibitors*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D012260:Ribonucleases / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D012260:Ribonucleases; C411110:rapLR1 enzyme