A monoclonal antibody that targets a protein expressed on the newly-formed blood cells of solid tumours has shown early promise as a therapeutic approach in a range of cancers.
Writing in the Journal of Clinical Oncology (2007; 25: 540-547), US researchers from Weill Medical College of Cornell University and Albany Medical Centre, New York, conducted a Phase I trial with J591, an antibody targeting the extracellular domain of
prostate-specific membrane antigen, in patients with advanced solid tumour malignancies.
PSMA expression is associated mainly with prostate cancer but high levels of the protein are also found in the neovasculature of a variety of solid tumours. The US trial was a proof-of-principle evaluation of PSMA as a potential neovascular target, with targeting, toxicity, maximum tolerated dose, pharmacokinetics and human anti-human antibody response as the primary endpoints.
Among the 27 patients who were given J591, 20 were shown to have at least one area of known metastatic disease targeted by the monoclonal antibody, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal and pancreatic cancers as well as melanoma. The J591 antibody targeted lung metastases in 13 of 18 patients with lung cancer. No HAHA responses were observed and the treatment was well tolerated.
The “excellent” targeting of known sites of metastases, combined with acceptable toxicity, suggest a potential role for J591 as a vascular-targeting agent in advanced solid tumours, the authors concluded.