Algeta demonstrates targeted cancer-killing potential of novel alpha particle linked antibodies
Preclinical studies show 227Th-rituximab more effective at killing CD20-positive lymphoma cells than 90Y-tiuxetan-ibritumomab (Zevalin)
Algeta ASA announced that a research paper showing the potential of its TH-1 technology for targeted cancer therapy has been published by "Blood", the official journal of the American Society of hematology (ASH).
Algeta's TH-1 technology links Thorium-227, which emits alpha particles, to cancer-targeting molecules such as antibodies. Alpha-emitting radionuclides are of considerable interest in the treatment of cancer as they are highly destructive to tumour cells but have very short range. Linking this radionuclide to tumour-seeking molecules creates a conjugate with the potential to specifically seek and destroy cancers while leaving surrounding healthy tissues undamaged.
The Blood paper describes how researchers from the Norwegian Radium Hospital (Oslo) in collaboration with Professor Oliver Press at the Fred Hutchison Cancer Research Center (Seattle, USA) and Algeta have linked Thorium-227 to the monoclonal antibody rituximab to create 227Th-rituximab and demonstrated its potent anti-tumour effects.
Rituximab binds to a specific molecule on the cancer cell surface called CD20 and is marketed in USA as Rituxan® by Genentech and Biogen-Idec for the treatment of certain types of non-Hodgkin's lymphoma (NHL) and rheumatoid arthritis, and as MabThera® by Roche for the treatment of certain types of NHL. Rituximab-based therapies generated global sales of nearly $6 billion in 2006.
In in vitro studies 227Th-rituximab killed CD20-positive lymphoma cells at low doses (Bq/ml) while in preclinical models, a single injection of 227Th-rituximab induced complete tumor regression in up to 60% of tumours without apparent toxicity.
According to the company, therapy with 227Th-rituximab was significantly more effective than the control radioimmunoconjugate 227Th-trastuzumab, which does not bind CD20, and the standard beta particle emitting radioimmunoconjugate for CD20-positive lymphoma, Zevalin® (90Y-tiuxetan-ibritumomab), which is marketed by Biogen-Idec.
Original publication: Dahle, J. et al.; "Targeted cancer therapy with a novel low dose rate alpha-emitting radioimmunoconjugate"; Blood 2007.
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