Release of cytokines and soluble cell surface molecules by PBMC after activation with the bispecific antibody CD3 x CD19.
Bispecific antibodies (BsAb) consist of two different heavy and light chains and may bind to two different antigens present on different cell types. With their dual specificity BsAb may recognize effector cells (e.g. T cells) on one hand and tumour cells (e.g. malignant B cells) on the other hand. The authors analysed whether T cell activation and subsequent killing of malignant B cells mediated by the bispecific antibody CD3 x CD19 was reflected by the release of cytokines. In addition, the authors investigated whether the in vitro cytokine release was similar to that observed in vivo in the patients treated with BsAb. The in vitro release of cytokines into the supernatant of cell cultures of peripheral blood mononuclear cells (PBMC) and malignant B cells was measured after incubation with either the bispecific antibody CD3 x CD19 or the monospecific anti-CD3 (aCD3) antibody in the presence or absence of interleukin (IL)-2. Release of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, IL-8, IL-10, soluble (s) CD4, sCD8 and sCD25 by PBMC was equal under both conditions and could be used as an indicator for T cell activation. However, the cytokine pattern and level did not correlate with the cytotoxic capacity, which was 4 logs higher with BsAb + IL-2 compared to aCD3 + IL-2. The in vitro pattern of cytokine release was similar to that observed in vivo in the serum of patients treated with BsAb and IL-2, indicating the possibility of predicting cytokine release in future patients with other therapeutic regimens.
Klein
S C
SC
Department of Immunology, University Hospital, Utrecht, The Netherlands.
Boer
L H
LH
de Weger
R A
RA
de Gast
G C
GC
Bast
E J
EJ
D018033:Antibodies, Bispecific / Q000276:immunology* / Q000494:pharmacology; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis / Q000502:physiology*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000502:physiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018033:Antibodies, Bispecific; D018941:Antigens, CD19; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D007378:Interleukins; D008222:Lymphokines; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma