Therapeutic Antibodies and Immunologic Conjugates
Summary of Key Points
• Because of their tumor selectivity, monoclonal antibodies offer exceptional opportunities for targeted therapy.
• When naked, monoclonal antibodies can kill tumors by receptor blockade and by actively inducing apoptosis.
• Tumor cytotoxicity is mediated through white cells by activating antibody-dependent cell-mediated cytotoxicity, and in the presence of serum, by complement-mediated cytotoxicity.
• Bispecific or multifunctional constructs can greatly enhance the antitumor effect of antibodies.
• Antibodies can deliver effector molecules in the form of drug conjugates, radioimmunoconjugates, immunocytokines, immunotoxins, immunoenzymes, immunoliposomes, and retargeted killer cells.
• Naked antibodies generally do not have overlapping toxicity profiles with chemotherapy and radiation therapies, and dose-limiting toxicities of immunoconjugates vary depending on the cytotoxic moiety (e.g., myelosuppression in radioimmunoconjugates) being used.
• Antibodies are likely to be most beneficial at the time of minimal residual disease, especially when used in conjunction with standard therapy.
• The following antibodies are licensed by the Food and Drug Administration and are in use for the cancers listed (target molecule in bold):
Alemtuzumab (Campath): B-chronic lymphocytic leukemia (CD52)
Bevacizumab (Avastin): colorectal cancer (VEGF)
Cetuximab (Erbitux): colorectal cancer, head and neck cancer (EGFR)
Ibritumomab (Zevalin): non-Hodgkin lymphoma (Yttrium-90, CD20)
Rituximab (Rituxan): non-Hodgkin lymphoma (CD20)
Trastuzumab (Herceptin): breast cancer (HER2)
Ipilimumab (Yervoy): melanoma (CTLA4)
Ofatumumab (Arzerra): CLL (CD20)
