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Table 1. Therapeutic antibodies for cancer treatment
Class Generic name Brand name Subtype Target FDA approval Major indication
Chimeric Ab Rituximab Rituxan IgG1k CD20 1997 CD20+ non-Hodgkin lymphoma
Brentuximab vedotin Adcetris IgG1 CD30 2011 Hodgkin lymphoma
Cetuximab Erbitux IgG1k EGFR 2004 Colon cancer
Dinutuximab Unituxin IgG1k GD2 2015 Neuroblastoma
Humanized Ab Trastuzumab Herceptin IgG1k HER2 1998 HER2+ Breast cancer
Gemtuzumab ozogamicin Mylotarg IgG4k CD33 2017 Acute myeloid leukemia
Bevacizumab Avastin IgG1k VEGF 2004 Colorectal cancer
Mogamulizumab Poteligio IgG1k CCR4 2018 CCR4+ Adult T cell leukemia lymphoma
Pertuzumab Perjeta IgG1k HER2 2012 HER2+ Breast cancer
Trastuzumab emtansine Kadcyla IgG1k HER2 2013 HER2+ Breast cancer
Obinutuzumab Gazyva IgG1k CD20 2013 Chronic lymphatic leukemia
Pembrolizumab Keytruda IgG4k PD-1 2014 Non-small cell lung cancer
Elotuzumab Empliciti IgG1k SLAMF7 2015 Multiple myeloma
Atezolizumab Tecentriq IgG1k PD-L1 2016 Urothelial cancer
Inotuzumab ozogamicin Besponsa IgG4k CD22 2017 Acute lymphatic leukemia
Human Ab Panitumumab Vectibix IgG2k EGFR 2006 Colorectal cancer
Ofatumumab Aezerra IgG1k CD20 2009 Chronic lymphatic leukemia
Ipilimumab Yervoy IgG1k CTLA4 2011 Malignant melanoma
Ramucirumab Cyramza IgG1 VEGFR2 2014 Gastric cancer
Nivolumab Opdivo IgG4 PD-1 2015 Malignant melanoma
Necitumumab Portrazza IgG1k EGFR 2015 Non-small cell lung cancer
Daratumumab Darzalex IgG1k CD38 2015 Multiple myeloma
Olaratumab Lartruvo IgG1 PDGFR 2016 Soft tissue sarcoma
Avelumab Bavencio IgG1l PD-L1 2017 Merkel cell carcinoma
Durvalumab Imfinzi IgG1k PD-L1 2017 Urothelial cancer
Unclassified Ab Cemiplimab Libtayo IgG4 PD-1 2018 Cutaneous squamous cell carcinoma

conjugates (ADCs), in which cytotoxic anticancer drugs are bound to antibody drugs, and immune
checkpoint inhibitors (ICIs) that cause binding inhibition of immune checkpoint molecules has been
rapidly advancing.

PHARMACOGENOMICS OF CANCER THERAPEUTIC ANTIBODIES
Antibody drugs show anti-tumor effects by binding to antigens in vivo, but because they are proteins with a
large molecular weight of about 150 kDa, they have complex pharmacokinetic and metabolic pathways that
are completely different from small molecule compounds. Small molecule compounds generally have good
[4]
membrane permeability and a large distribution volume (Vd) because they are distributed in cells . Since
the effects of metabolism and excretion pathways are large for each drug, many pharmacogenetic studies
have been conducted on the effects of polymorphisms of cytochrome P450 and ABC transporter on blood
concentration levels of drugs. However, in the case of antibody drugs, the Vd is relatively small, they do
not undergo metabolism such as by cytochrome P450, and the main elimination route is the digestion of
amino acids in cells. For these reasons, they exhibit very different pharmacokinetics from small molecule
compounds, and there are still many unknowns. A detailed description of the pharmacokinetics of
antibody drugs was given by the critical review of Liming Liu, and this section outlines pharmacogenomic
[5]
factors that affect the efficacy and pharmacology of antibody drugs .
Neonatal Fc receptor
The neonatal Fc receptor (FcRn) encoded by FCGRT was assumed in the 1960s to be a receptor that protects
[6,7]
IgG from catabolism by Roger Brambell . After cloning of FcRn by Simister & Mostov in 1989, analysis of
[8,9]
knockout mice by Roopenian & Akilesh proved its function in 2007 . The current understanding of FcRn
is that blood circulating IgG is taken up by vascular endothelial cells and monocytes by pinocytosis and
receptor-mediated endocytosis. Thereafter, IgG binds to FcRn in endosomes in an acidic environment (pH