Current Perspectives on Therapeutic Antibodies

Since the first monoclonal antibody, muromonab-CD3, was approved for therapeutic use in 1986, numerous molecules have been targeted using therapeutic antibody technology, resulting in 26 therapeutic antibodies being approved by the US FDA as of November, 2009. Initial concerns regarding antibody drugs focused on immunogenicity, short serum half-life, and weak efficacy. As the types of antibodies progressed from murine to chimeric, humanized, and fully human antibodies, great progress has been made in immunogenicity and in vivo instability issues. For example, humanized antibodies, such as bevacizumab, exhibit less than 0.2% immunogenicity and a 20 day serum half-life, which is comparable to native immunoglobulin. Some recently developed antibodies are exceedingly efficacious and have become first-line therapy for their target diseases. Here, we address and analyze all clinically approved therapeutic antibodies to date by discussing immunogenicity, half-life, and efficacy.*GEN ROCH, 2010, ACT PRESCR INFMartinelli E, 2009, CLIN EXP IMMUNOL, V158, P1, DOI 10.1111/j.1365-2249.2009.03992.xLachmann HJ, 2009, NEW ENGL J MED, V360, P2416Rivkin A, 2009, CLIN THER, V31, P1158, DOI 10.1016/j.clinthera.2009.06.015*CENT, 2009, SIMP FULL PRESCR INF*ASCO, 2009, AM SOC CLIN ONC ASCO*GLAXOSMITHKLINE, 2009, ARZ FULL PRESCR INF*NOV, 2009, IL FULL PRESCR INF*EMEA, 2009, SUMM PROD CHARWang D, 2008, HEALTH TECHNOL ASSES, V12, P1Swann PG, 2008, CURR OPIN IMMUNOL, V20, P493, DOI 10.1016/j.coi.2008.05.013Lichtenstein GR, 2008, GASTROENTEROLOGY, V134, pA68*UCB, 2008, CIMZ FULL PRESCR INFRoopenian DC, 2007, NAT REV IMMUNOL, V7, P715, DOI 10.1038/nri2155*AL PHARM, 2007, SOL FULL PRESCR INFHillmen P, 2006, NEW ENGL J MED, V355, P1233Bourhis J, 2006, J CLIN ONCOL, V24, P2866, DOI 10.1200/JCO.2005.04.3547KACSKOVICS Z, 2006, INT IMMUNOT, V18, P525*GEN, 2006, LUC FULL PRESCR INF*AMG, 2006, VECT FULL PRESCR INFThienelt CD, 2005, J CLIN ONCOL, V23, P8786, DOI 10.1200/jco.2005.03.1997Hwang WYK, 2005, METHODS, V36, P3, DOI 10.1016/j.ymeth.2005.01.001Saltz LB, 2004, J CLIN ONCOL, V22, P1201, DOI 10.1200/JCO.2004.10.182*IMCL SYST, 2004, AV FULL PRESCR INF*IMCL SYST, 2004, ERB FULL PRESCR INF*BIOG IDEC, 2004, TYS FULL PRESCR INFWitzig TE, 2003, J CLIN ONCOL, V21, P1263, DOI 10.1200/JCO.2003.08.043*GEN, 2003, RAPT FULL PRESCR INF*GEN, 2003, XOL FULL PRESCR INFWitzig TE, 2002, J CLIN ONCOL, V20, P3262, DOI 10.1200/JCO.2002.11.017*ABB, 2002, HUM FULL PRESCR INF*BIOG IDEC, 2002, ZEV FULL PRESCR INFKaminski MS, 2001, J CLIN ONCOL, V19, P3918Tcheng JE, 2001, CIRCULATION, V104, P870*MILL LEX, 2001, CAMP FULL PRESCR INF*WYETH, 2000, MYL FULL PRESCR INF*GEN, 1998, HERC FULL PRESCR INF*CENT, 1998, REM FULL PRESCR INF*NOV, 1998, SIM FULL PRESCR INF*MED, 1998, SYN FULL PRESCR INF*GEN, 1997, RIT FULL PRESCR INF*PROT DES LAB, 1997, ZEN FULL PRESCR INFThurmann P, 1996, PHARMACOECONOMICS, V9, P417KUUSREICHEL K, 1994, CLIN DIAGN LAB IMMUN, V1, P365NORMAN DJ, 1993, TRANSPLANT P, V25, P89FRODIN JE, 1992, CELL BIOPHYS, V21, P153LEITHA T, 1991, CHEST, V99, P14RIVA P, 1989, NUCL MED BIOL, V16, P659LEDERMANN JA, 1988, BRIT J CANCER, V58, P654