RESEARCH & DEVELOPMENT Immunotoxin LMB-l: antitumour activity in epithelial tumours

LMB-l is the first immunotoxin to show antitumour activity in epithelial tumours, say researchers in the US. In a phase I study that has so far involved 38 patients with advanced solid tumours resistant to conventional therapy, they observed objective antitumour activity in 5 patients, while another 18 study patients displayed stable disease.

LMB-l is composed of modified Pseudomonas exotoxin A linked to the monoclonal antibody B3. This antibody recognises a carbohydrate antigen that is present on few normal tissues but abundant on many human solid tumours. The toxicity of the exotoxin acting independently of B3 has been reduced to 0.5% of that of the native toxin by the removal of 2 amino acid domains, including its cell recognition domain.

One patient with metastatic breast cancer showed a complete remission lasting 2 months, and 1 with metastatic colon cancer showed a> 75% tumour shrinkage and no disease progression for 7 months.

Limitations of this therapy are the development of antibodies to the toxin and to B3, and adverse effects, predominantly a vascular leak syndrome, associated with higher doses. A phase I trial of a similar agent utilising only a portion of the B3 antibody is in progress.

Pai LH, Wittcs R, Setser A, Wtllingbam Me, Pastan I. Treaunent of advanced solid tumors with immunotoxin LMB-1: an antibody linkc:d to Pseudomonas exotoxin. Nature Medicine 2: 350-353, Mar 1996 800429480

0156-270319611030-00071$01.00" Adl. Internatlolllli Limited 11K16. All rights reHrvad INPHARMA- 30 Mar 11K16 No. 1030

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