PMID: 7543021Jun 1, 1995Paper

CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma

Cancer Immunology, Immunotherapy : CII
G C de GastA Van Dijk

Abstract

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed a t1/2 of 10.5 h with peak levels of 200-300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor alpha was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon gamma. IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1 beta in serum). No gross changes in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3 x CD19 bsAb only moderate toxicity was found, probably due to CD...Continue Reading

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Citations

May 10, 2007·Cancer Immunology, Immunotherapy : CII·Freddy Tita-NwaMartin Kornacker
Feb 17, 2009·Journal of Experimental & Clinical Cancer Research : CR·Michael A StröhleinMarkus M Heiss
Nov 5, 2011·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Lawrence G Lum, Archana Thakur
Sep 1, 2008·Expert Opinion on Drug Discovery·Lawrence G Lum, Zaid Al-Kadhimi
Feb 5, 2019·Current Oncology Reports·Roberta Demichelis-GómezChristianne Bourlon
Apr 22, 2020·Cellular & Molecular Immunology·Heliang LiErwei Song
Nov 27, 2018·Southern African Journal of HIV Medicine·Brian T FlepisiBernd Rosenkranz
Apr 5, 2016·Biochemical and Biophysical Research Communications·Chia-Yen LuChuan-Lung Hsu

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