期刊
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
卷 24, 期 2, 页码 155-161出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/cbr.2009.0627
关键词
antibody; affinity; avidity; tumor targeting; internalization; scFv; specificity
类别
资金
- National Cancer Institute [NCI 5RO1 CA118159]
Many factors contribute to successful tumor targeting by antibodies. Besides properties of the tumor tissue and general antibody pharmacology, a relationship exists between an antibody and its antigen that can shape penetration, catabolism, specificity, and efficacy. The affinity and avidity of the binding interactions play critical roles in these dynamics. In this work, we review the principles that guide models predicting tumor penetration and cellular internalization while providing a critical overview of studies aimed at experimentally determining the specific role of affinity and avidity in these processes. One should gain the perspective that binding affinity can, in part, dictate the localization of antibodies in tumors, leading to high concentrations in the perivascular space or low concentrations diffused throughout the tumor. These patterns can be simply due to the diminution of available dose by binding antigen and are complicated by internalization and degradation stemming from slow rates of dissociation. As opposed to the trend of simply increasing affinity to increase efficacy, novel strategies that increase avidity and broaden specificity have made significant progress in tumor targeting.
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