Blood. 2005 Dec 15;106(13):4308-14. Epub 2005 Aug 18.Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin.Chang CH, Sapra P, Vanama SS, Hansen HJ, Horak ID, Goldenberg DM. Immunomedics, Morris Plains, NJ, USA. Ranpirnase is a cytotoxic ribonuclease
(RNase) isolated from frog oocytes. Here we describe high antitumor
activity of a novel immunotoxin, 2L-Rap-hLL1-gamma4P, composed of
2 Rap molecules, each fused to the N terminus of the light chain of
hLL1, an internalizing anti-CD74 humanized antibody. To reduce unwanted
side effects, the constant region of hLL1 was changed from gamma1
to gamma4 and further to gamma4P by replacing serine228 to proline
to prevent the formation of a half immunoglobulin G (IgG) common for
IgG4. In vitro, 2L-Rap-hLL1-gamma4P retained RNase activity, specific
binding to CD74, and was significantly more potent against CD74+ cell
lines (Daudi, Raji, and MC/CAR) than naked hLL1. In vivo, the pharmacokinetic
profile of 2L-Rap-hLL1-gamma4P was similar to that of naked hLL1.
The maximum tolerated dose of 2L-Rap-hLL1-gamma4P in severe combined
immunodeficient mice (SCID) or BALB/c mice was 50 microg per mouse.
In Raji and Daudi Burkitt lymphoma xenograft models, treatment with
a single 5 to 50 microg dose of 2L-Rap-hLL1-gamma4P, given as early
or delayed treatment, resulted in cures of most animals. Treatment
with 2L-Rap-hLL1-gamma4P was significantly better than all controls,
including saline, naked hLL1, and nonspecific immunotoxin. In conclusion,
2L-Rap-hLL1-gamma4P demonstrated excellent in vitro and in vivo efficacy
and thus merits further consideration as a therapeutic for CD74+ tumors. If you have mesothelioma, we might be able to help you. Fill out this form. This website is sponsored by Jonathan David* of The
David Law Firm. The David Law Firm is located in The Woodlands, Texas
(Greater Houston Area) and can be reached toll free at 1-800-998-9729
for more information on mesothelioma. Jonathan David is not a medical
doctor. The information on these pages is for the education of mesothelioma
patients and their families regarding potential medical and legal
options. Patients are advised to consult with a medical doctor.
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a clinical practice guideline.
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