CATIONIZATION OF A MONOCLONAL-ANTIBODY TO THE HUMAN-IMMUNODEFICIENCY-VIRUS REV PROTEIN ENHANCES CELLULAR UPTAKE BUT DOES NOT IMPAIR ANTIGEN-BINDING OF THE ANTIBODY

Replication of the human immunodeficiency virus (HIV) within cells may be blocked by neutralization of viral-specific proteins that are abso lutely required for growth of the virus. One such viral-specific prote in is REV, and a monoclonal antibody (mAb) against the REV protein is a potential therapeutic for acquired immune deficiency syndrome (AIDS) . However, in order to effect 'intracellular immunization', mAbs must be enabled to target the intracellular compartment. One strategy for t ranscellular drug delivery of mAb-based therapeutics is cationization, and the present studies describe the cationization of a murine mAb sp ecific to the REV protein of HIV-1. The isoelectric point (pI) of the mAb was raised from 6.6 to more than 9.5. There was virtually no diffe rence in binding to wild-type REV protein between the native or cation ized anti-REV mAb, based on studies with a solid-phase immunoradiometr ic assay. The uptake of the [I-125] native anti-REV mAb by human perip heral blood lymphocytes (PBLs) was negligible; however, there was a ma rked increase in both total cell binding and endocytosis by the human PBLs of the [I-125] cationized anti-REV mAb. In conclusion, these stud ies show that an anti-REV mAb may be cationized to markedly increase e ndocytosis of the antibody and that this cationization reaction does n ot significantly alter the affinity of the antibody for its target pro tein. Cationized anti-REV mAbs may allow for intracellular immunizatio n of the virus and are potential therapeutics for the treatment of HIV .