Anti-FR Antibody Generation and Engineering: Development of New Therapeutic Tools

Abstract

The discovery of the methodology to raise mouse monoclonal antibodies (mAbs) represents a milestone in the history of medicine and has opened the way to antibody therapy development. In the oncologic field, antibody-based therapy seems an attractive strategy for those tumors, such as epithelial ovarian cancer and glioblastoma, for which the existing treatment options are still not sufficient. Initial clinical trials with mouse mAbs enlighten, as major limitations, their xenogenic origin and their dimension. Thus, in order to optimize mAb clinical therapeutic applications, genetic engineering was developed to: (1) generate chimeric, humanized, and human mAbs starting from mouse mAbs; (2) reshape antibody format; (3) increase antibody efficacy. The history of anti-human folate receptor (FR)α mAb generation and its modification paralleled that of genetic engineering of mAbs. At least three anti-FRα mAbs (MOv18, MOv19, and LK26) and their derivatives have reached advanced levels of development. In this chapter, the most relevant preclinical and clinical results obtained with them are widely discussed. Also, published data related to anti-FRβ mAb are reported. Full exploitation of the described anti-FRα antibody-based reagents, however, awaits the confirmation of promising drug safety and clinical efficacy from well-designed, randomized clinical trials.