Cell-penetrating peptides and antibodies: a new direction for optimizing radioimmunotherapy

Excerpt

Owing to their highly specific recognition of cognate antigens, antibodies have long been dream vehicles for targeted therapy and have recently been used to deliver radionuclides, drugs, toxins, and enzymes. Radioimmunotherapy (RIT) is an attractive therapeutic modality that combines the specificity of antibodies to antigens with the toxicity of the radionuclides. Radiolabeled antibodies like Bexxar and Zevalin have been approved by the FDA and are being used successfully to treat hematological malignancies in clinics. Moreover, because of their ability to inhibit the functional activity of the target antigen, some antibodies are also being used as unarmed therapeutics for solid tumors. Examples of these antibodies in clinics are: Avastin, an anti-VEGF monoclonal antibody that is used in the therapy of colorectal cancer, and Herceptin, an anti-Her2 antibody approved for the therapy of Her2-overexpressing metastatic breast and other cancers. For solid tumors, however, radiolabeled antibody-based therapeutics have had limited success, primarily owing to slow uptake, poor penetration, and inadequate retention. Recent research efforts have centered on the strategies to overcome these limitations and optimize tumor uptake of armed antibodies. Several recent articles, including one from Hu et al. in the March 2007 issue of EJNMMI [1], have described the possibility of using cell-penetrating peptides for the intracellular delivery of radiolabeled antibodies to target intracellular epitopes and improve tumor uptake and retention. …