The incidence of immunogenicity in clinical trials of humanized and fully-human antibodies is generally low but adverse reactions can still pose a significant safety risk.Recent clinical data for novel therapeutic antibodies used in the treatment of cancer (e.g.anti-PSMA) and infection (e.g.anti-anthrax protective antigen) support the concept that the avoidance or removal of helper T cell epitopes in variable regions of therapeutic antibodies reduces the incidence of immunogenicity.Preclinical immunogenicity data will be presented for a variety of therapeutic antibodies (chimeric, humanized and "fully human") which is based on the frequency and potency ofT cell epitopes present in V-region sequences.These data have been used to provide an early assessment for the relative risk of immunogenicity between different antibody therapeutics.Furthermore, in a refinemeut of this process novel humanized antibodies against CD20 and V3 have been generated in which T cell epitopes in V-region sequences have been avoided resulting in therapeutic antibodies with reduced immunogenic potential.