RESUMO
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non-Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell-engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.
Assuntos
Anticorpos Biespecíficos/administração & dosagem , Antineoplásicos/administração & dosagem , Linfoma de Células B/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Linfócitos T Citotóxicos/imunologia , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Linfócitos B/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Contagem de Linfócitos , Linfoma de Células B/imunologia , Linfoma Folicular/imunologia , Linfoma de Célula do Manto/imunologia , Recidiva , Linfócitos T/imunologiaRESUMO
AIM OF THE STUDY: Adecatumumab (also known as MT201) is a human recombinant IgG1 monoclonal antibody binding with low affinity to epithelial cell adhesion molecule (EpCAM). To explore safety, pharmacokinetics and pharmacodynamics of adecatumumab, a phase I trial in patients with hormone refractory prostate cancer (HRPC) was performed. METHODS: Twenty patients were treated with two adecatumumab infusions on days 0 and 14 in cohorts with doses of ten up to 262 mg/m2. RESULTS: Adecatumumab was well tolerated at all doses tested, and no maximum tolerated dose reached. Most adverse events were mild or moderate with pyrexia and nausea being most frequent. The highest dose of adecatumumab induced shortly after infusion robust and transient increases of TNF-alpha serum levels. At all doses, significant transient declines of peripheral natural killer cells were observed shortly after antibody infusions. Adecatumumab had a serum half-life of 15 days, and immune responses to the antibody were not detected. CONCLUSIONS: A benign safety profile, long serum half-life and low immunogenicity do warrant further exploration of adecatumumab for treatment of EpCAM-expressing neoplasia.
