Monoclonal antibody pharmacogenomics in cancer treatment

Abstract

Conventionally, in the pharmacokinetic/pharmacodynamic analysis of small molecule compounds such as cytotoxic anticancer drugs, polymorphism analysis of genes related to absorption, distribution, metabolism, and excretion has been performed in addition to the analyses of blood concentrations of drugs. Such pharmacogenetic factors play an important role in predicting therapeutic effects and adverse events and in the proper use of drugs. With the recent launch of immune checkpoint inhibitors (ICIs) and the rapid development of antibody-drug conjugates (ADCs) currently underway, there is no doubt that antibody drugs, which are large molecule compounds, will become key drugs in anticancer drug treatment. However, the pharmacokinetic and pharmacodynamic analysis of antibody drugs is still not sufficient, and further elucidation of factors and mechanisms affecting their dynamics in the human body is necessary. Moreover, the pharmacogenomic factors of antibody drugs have not yet been fully studied. There are many factors that should be clarified, such as factors that regulate the host immune response in ICI therapy and the effects of ATP-binding cassette transporter and cytochrome P450 on the payload of ADCs. This review provides an outline of antibody drugs in cancer treatment and summarizes the pharmacogenomic factors of antibody drugs known to date.

Overview of current approaches in cancer immunotherapy and personalized opportunities for future aspect

“…In the first class, there are unconjugated bare mAbs such as Alemtuzumab and Transtuzumab associated with antigens on cancer cells, and in the second class mAbs are conjugated with chemotherapeutic drugs or radioactive isotope Gemtuzumab ozogamycin is an example of conjugated mAbs, and Ibritumomab tiuxetan is an example of (radionuclides) radioactive conjugated mAbs. There are also bispecific antibodies (BsAb) called Blinatumomab, which contain two different mAbs and can bind two different antigens simultaneously (Özlük et al, 2017;Kimiz Gebologlu et al, 2018;Riley et al, 2019;Kozani et al 2021;Yagishita and Hamada, 2019). Nanoantibodies: One of the challenges in immunotherapy is to design dendritic cells to target TAA and provide effective immunization against the tumor.…”

“…Monoclonal antibodies approved for cancer treatment(Kimiz Gebologlu et al, 2018;Kozani et al 2021;Yagishita and Hamada, 2019) …”