Explore into Pharmacokinetics/pharmacodynamics (PK/PD) of Antibody Drugs

In the past few decades, both pharmaceutical companies and academia have spent much financial
resources and energy to improve the practicability and accuracy of in vitro screening technology that
can test the biological activity and physicochemical properties of compounds. However, the study of
potential drug candidates in animal models remains disposable.

FDA, NMPA, and other regulatory agencies require that before the drug enters the clinic, its
effectiveness and safety must be assessed in animals. An animal, whether a rat, a dog, a monkey, or
even a human, is a complex biological system. At present, there is no in vitro screening method or
combined method that can mimic and reflect the complexity of the entire organism. Therefore, it is
indispensable to use animal models to evaluate the effects of candidate drugs on humans and diseases.

Classification of tumor animal models

Mouse xenograft tumor model

Among the tumor disease models, the mostly used is the mouse xenograft tumor model that utilizes
specific mice, such as SCID, NSG, B-NDG mice, and other conventional immunodeficiency or severe
immunodeficiency mice, which cannot produce immune attacks on foreign cells.

* CDX (Cell-line-derived Xenograft) model: Standardized cancer cell lines are used for modeling. The
cells are easy to obtain but have drawbacks that they cannot represent the original clinical tumor.
* PDX (Patient-derived Xenograft) model: Tumor tissue or cells obtained from tumor patients with the
characteristics of clinical tumors.

Most antibody drugs kill tumors by mediating the immune system, so to evaluate their effectiveness, it
is necessary to reconstitute an animal model of the human immune system (including DC, B, T, and
NK).

Mouse allograft tumor model

The disadvantage of the xenotransplantation model is that the use of immunodeficient mice for
modeling may result in the rejection of the immune system caused by cross-species transplantation.
The allograft tumor model allows researchers to use a mouse model with a sound immune system but
requires the mouse tumor cell lines for modeling studies. The fully functional immune system makes
the allograft model better than the xenograft model to simulate the real situation of cancer.

* Wild mouse allotransplantation model: mainly used in the pharmacological and pharmacological
study of Surrogate antibody.
* Genetically modified/humanized mouse model: for the study of humanized antibodies.

Research on the Biomarkers of Antibody Drugs Using Genetically Humanized Mice

The core of PD/PK evaluation is the determination of suitable biomarkers.
1. Target biomarkers
2. Mechanism biomarker: detection of the tumor microenvironment (biomarker profiling)
* Changes in the number, location, and status (e.g., activation, dysfunction) of immune cells in the
tumor
* Changes in the number of tumor cells and status
3. Toxicity biomarkers
The study of metabolism of antibody drug using genetically humanized mice is different from that of
small molecule drugs. The factors that affect antibody pharmacokinetics are:
* Fcγ receptor
* FcRn cycle
* Absorption and metabolism
* Immunogenicity
* TMDD (target-mediated drug disposal)

midbody Ribosome and Alzheimer's Disease

Investigation of Pharmacokinetics/pharmacodynamics (PK/PD) of Antibody Drug

Pharmaceutical corporations and academic institutions have invested significant time, money, and
effort in recent years to increase the accuracy and applicability of in vitro screening technology, which
measures the biological activity and physicochemical characteristics of substances. Animal models are
still used in the investigation of possible medication candidates, nevertheless.

FDA, NMPA, and other regulatory bodies demand that a drug's efficacy and safety be evaluated in
animals before it is allowed on the market. An animal is a sophisticated biological system, whether it
be a rat, dog, monkey, or even a person. There is currently no in vitro screening technique or combined
technique that can accurately represent and simulate the complexity of the complete organism.
Therefore, using animal models to assess the effects of potential medications on humans and diseases is
essential.

classification of animal models for tumors

Mouse Xenograft tumor model

The mouse xenograft tumor model, which uses certain animals like SCID, NSG, B-NDG, and other
conventional immunodeficiency or severe immunodeficiency mice, who cannot produce immune
attacks on foreign cells, is the most widely used tumor disease model.

* Standardized cancer cell lines are employed for the CDX (Cell-line-derived Xenograft) model.
Although the cells are simple to get, one disadvantage is that they cannot accurately mimic the initial
clinical tumor.
* PDX (Patient-derived Xenograft) model: cells or tumor tissue from cancer patients that exhibit the
traits of actual tumors.

Most antibody drugs kill tumors by mediating the immune system, so to evaluate their effectiveness, it
is necessary to reconstitute an animal model of the human immune system (including DC, B, T, and
NK).

Mouse allograft tumor model

The use of immunodeficient mice for modeling could lead to immune system rejection brought on by
cross-species transplantation, which is a drawback of the xenotransplantation model. Although the
mouse tumor cell lines are needed for modeling studies, the allograft tumor model enables researchers
to employ a mouse model with a healthy immune system. The allograft model outperforms the
xenograft model in simulating the actual cancer situation thanks to its fully working immune system.

* Wild mouse allotransplantation model: mainly used in the pharmacological and pharmacological
study of Surrogate antibody.

* Genetically modified/humanized mouse model: for the study of humanized antibodies.