Performance of CD3xCD19 bispecific monoclonal antibodies in B cell malignancy.
Bispecific monoclonal antibodies, with a dual specificity for tumor associated antigens on target cells and for surface markers on immune effector cells, have been shown (in vitro) to be effective in directing and triggering effector cells to kill target cells resulting in target cell lysis. Bispecific monoclonal antibodies (BsAb) against the CD3 antigen on T cells and the CD19 antigen on B cell were developed. Data obtained by in vitro experiments might indicate that clinical responses in BsAb immunotherapy, will only be obtained in patients with minimal tumor load, and may need additional T cell stimulation via cytokines such as IL-2. Although these experiments have shown us their limitations, they also include the promise of BsAb-directed immunotherapy in B cell malignancy as further demonstrated during a Phase I trail, showing little toxicity. Clearly, much remains to be done before this BsAb is routinely used for therapy, but, the results presented show that the CD3xCD19 BsAb has a potential as a therapeutic agent in B cell malignancy. This report describes the experiments performed to test a new immunotherapeutic approach for the treatment of B cell malignancy. Bispecific antibodies are described that can target cytotoxic T cells to tumor cells and elicit a cytolytic action towards these cancer cells.
Haagen
I A
IA
Department of Immunology, University Hospital Utrecht, The Netherlands.
D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D018941:Antigens, CD19 / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D015448:Leukemia, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D014411:Neoplastic Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014410:Tumor Stem Cell Assay
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D007376:Interleukin-2; D016853:Muromonab-CD3