Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopes.

ABSTRACT: Many nonhuman proteins have useful pharmacological activities, but are infrequently effective in humans because of their high immunogenicity. A recombinant immunotoxin (HA22, CAT8015, moxetumomab pasudotox) composed of an anti-CD22 antibody variable fragment fused to PE38, a 38-kDa portion of Pseudomonas exotoxin A, has produced many complete remissions in drug-resistant hairy-cell leukemia when several cycles of the agent can be given, but has much less activity when antibodies develop. We have pursued a strategy to deimmunize recombinant immunotoxins by identifying and removing B-cell epitopes. We previously reported that we could eliminate most B-cell epitopes using a combination of point mutations and deletions. Here we show the location and amino acid composition of all of the B-cell

SUBMITTER: Onda M 

PROVIDER: S-EPMC3078343 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature