Patent Evaluation: Chimaeric Polypeptides as Anti-HIV Agents

Summary

Novelty: Chimaeric polypeptides comprising the CD4 receptor protein (recognized by HIV gp120) linked to a CD3-recognized antigen (stimulating cytotoxic CD3⁺ T-cells) are disclosed. These proteins are potentially able to elicit cytotoxic T-cell-mediated killing of HIV virus and infected cells, and are also of low molecular weight and thus may be produced by prokaryote expression. This stimulation of cytotoxic activity may also be potentially useful for the treatment of tumours.

Biology: Characterization of the claimed polypeptides was performed in in vitro culture of HIV infected/noninfected Jurkat cells labelled with ⁵¹Cr cocultured with a CD3⁺ cytotoxic T-cell clone; the polypeptide designated CD4-FvCD3-C_κ showed maximal discriminant killing of the HIV infected cells at a concentration of 1 μg/ml.

Chemistry: The chimaeric proteins are optionally linked to the constant C_κ or C_λ immunoglobulin light chain region. Full protein sequence data are also provided. Plasmid construction was by conventional recombinant methods, with transfection of J558L cells, purification of the exemplified protein CD4-FvCD3-C_κ was by immunoaffinity chromatography using an anti-C_κ antibody.