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Discovery of antibodies targeting the immune checkpoint protein PD-L1

Koetchatturat, Chirarat LU (2017) KBK820 20161
Pure and Applied Biochemistry
Abstract
Cancer figure among the leading causes of morbidity and mortality worldwide. Finding a treatment to defeat cancer is a challenging task but immunotherapy that aims to improve the patient´s own immune system seems to be a promising therapeutic approach. Cancer cells can develop different mechanisms to evade the immune system. One such resistance mechanism is the expression of PD-L1 protein on the surface of cancer cells. PD-L1 binds to the inhibitory immune checkpoint receptor PD-1 on T cells and this interaction has an inhibitory effect on the T cells. Also certain tumor-infiltrating immune cells such as macrophages overexpress PD-L1 and contribute to immune suppression. Blockade of the PD-1/PD-L1 pathway using monoclonal antibodies is one... (More)
Cancer figure among the leading causes of morbidity and mortality worldwide. Finding a treatment to defeat cancer is a challenging task but immunotherapy that aims to improve the patient´s own immune system seems to be a promising therapeutic approach. Cancer cells can develop different mechanisms to evade the immune system. One such resistance mechanism is the expression of PD-L1 protein on the surface of cancer cells. PD-L1 binds to the inhibitory immune checkpoint receptor PD-1 on T cells and this interaction has an inhibitory effect on the T cells. Also certain tumor-infiltrating immune cells such as macrophages overexpress PD-L1 and contribute to immune suppression. Blockade of the PD-1/PD-L1 pathway using monoclonal antibodies is one way of preventing suppression of immune responses caused by cancer cells allowing the immune system to fight cancer more efficiently and successfully. In this study monoclonal antibodies against PD-L1 were isolated. As a first step cell-bound and soluble target antigens, both human and mouse PD-L1, were prepared and quality controlled. Pools of antibodies were then isolated from a phage display based human antibody library using three cycles of selection. Antibodies were subsequently screened to characterize the binding specificity of individual clones by conventional ELISA and flow cytometry. Unique antibody clones were identified by DNA sequencing. A total of 101 unique antibodies that bind specifically to human and/or mouse PD-L1 were successfully isolated. 88 of these antibodies bind to PD-L1 when expressed on cells whereas the remaining 13 bind only to the soluble protein. The isolated panel of antibodies can be used for future functional studies in vitro and in vivo aiming to identify therapeutic drug candidates. (Less)
Popular Abstract
Cancer is a group of diseases with over 100 different types. Cancer is characterized as abnormal cells that divide without control and potentially spread to the surrounding tissues. In healthy individuals, old and damaged cells die in a process called programmed cell death. New cells replace old by normal cell division. Cancer cells in contrast are able to ignore signals from the body telling them to stop dividing and/or undergo programmed cell death.
The immune system is the defense system of the body. It protects the body from attacks by foreign microorganisms like bacteria, viruses, and fungi but also searches for abnormal human cells and kills them. The body most often kills cancer cells before they get the chance to grow into... (More)
Cancer is a group of diseases with over 100 different types. Cancer is characterized as abnormal cells that divide without control and potentially spread to the surrounding tissues. In healthy individuals, old and damaged cells die in a process called programmed cell death. New cells replace old by normal cell division. Cancer cells in contrast are able to ignore signals from the body telling them to stop dividing and/or undergo programmed cell death.
The immune system is the defense system of the body. It protects the body from attacks by foreign microorganisms like bacteria, viruses, and fungi but also searches for abnormal human cells and kills them. The body most often kills cancer cells before they get the chance to grow into tumors, but occasionally cancer cells evade the immune system in different ways. A method of treating cancer is immunotherapy, which recently has gained much attention for its effective results. Immunotherapy basically boosts the immune system and m akes it more efficient. One important player in immunotherapy is the monoclonal antibody, which can be used in different ways for defeating cancer cells: 1) Antibodies attach to cancer cells which help the immune system to spot cancers more easily, 2) Antibodies carry drugs or radiation for specific delivery to cancer cells, 3) Antibodies block signals telling cancer cells to divide, 4) Antibodies modify the activity of cells in the immune system.
This report describes the work to find possible antibody candidates from the fourth group. (Less)
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author
Koetchatturat, Chirarat LU
supervisor
organization
course
KBK820 20161
year
type
H2 - Master's Degree (Two Years)
subject
keywords
immunotherapy, cancer, antibodies, applied biochemistry, tillämpad biokemi
language
English
id
8896522
date added to LUP
2017-01-09 10:57:56
date last changed
2017-01-09 10:57:56
@misc{8896522,
  abstract     = {Cancer figure among the leading causes of morbidity and mortality worldwide. Finding a treatment to defeat cancer is a challenging task but immunotherapy that aims to improve the patient´s own immune system seems to be a promising therapeutic approach. Cancer cells can develop different mechanisms to evade the immune system. One such resistance mechanism is the expression of PD-L1 protein on the surface of cancer cells. PD-L1 binds to the inhibitory immune checkpoint receptor PD-1 on T cells and this interaction has an inhibitory effect on the T cells. Also certain tumor-infiltrating immune cells such as macrophages overexpress PD-L1 and contribute to immune suppression. Blockade of the PD-1/PD-L1 pathway using monoclonal antibodies is one way of preventing suppression of immune responses caused by cancer cells allowing the immune system to fight cancer more efficiently and successfully. In this study monoclonal antibodies against PD-L1 were isolated. As a first step cell-bound and soluble target antigens, both human and mouse PD-L1, were prepared and quality controlled. Pools of antibodies were then isolated from a phage display based human antibody library using three cycles of selection. Antibodies were subsequently screened to characterize the binding specificity of individual clones by conventional ELISA and flow cytometry. Unique antibody clones were identified by DNA sequencing. A total of 101 unique antibodies that bind specifically to human and/or mouse PD-L1 were successfully isolated. 88 of these antibodies bind to PD-L1 when expressed on cells whereas the remaining 13 bind only to the soluble protein. The isolated panel of antibodies can be used for future functional studies in vitro and in vivo aiming to identify therapeutic drug candidates.},
  author       = {Koetchatturat, Chirarat},
  keyword      = {immunotherapy,cancer,antibodies,applied biochemistry,tillämpad biokemi},
  language     = {eng},
  note         = {Student Paper},
  title        = {Discovery of antibodies targeting the immune checkpoint protein PD-L1},
  year         = {2017},
}