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Immunotherapy has become the "fifth pillar" of cancer treatment.
At present, the successful listing of immune checkpoint inhibitor drugs represented by PD-1/L1 and CTLA-4 at home and abroad has proved the clinical transformation potential of this treatment strategy.
And business value
.
However, immunotherapy is not a panacea.
The new immune checkpoint introduced today comes from the NKG2 family-NKG2A
.
NKG2 family proteins are a type of receptor in a complex receptor-ligand signaling network.
A potential immune checkpoint-NKG2A
NKG2A is an "inhibitory" member of the NKG2 family, which is mainly expressed in NK (natural killer) cells and NKT cells
.
NKG2A can bind to CD94 protein to form a heterodimer.
The natural ligand of NKG2A is the HLA-E molecule, and the expression of this molecule is very low under normal conditions
.
However, on the surface of most tumor cells, the expression of HLA-E increases, which inhibits the activity of NK cells, thereby preventing tumors from being killed by NK cells
NK cells are currently a hot research direction
.
As one of the most important immune cells in the body, NK cells are not only related to anti-tumor, anti-viral infection and immune regulation, they are also involved in the occurrence of hypersensitivity and autoimmune diseases, and are one of the strongest anti-cancer effects.
Schematic diagram of the action of NKG2A antibody (picture from reference 1)
Currently under research NKG2A monoclonal antibody
Recently, Shanghai Huaiyue Biotechnology Co.
, Ltd.
announced that the company's research immune checkpoint project NKG2A monoclonal antibody new drug clinical trial application (IND) has been approved in the United States
.
The NKG2A monoclonal antibody is expected to start enrollment of American patients in the second half of 2021.
In addition, there are two NKG2A target monoclonal antibody drugs entering the clinical stage worldwide, including AstraZeneca's monalizumab and Bristol-Myers Squibb (BMS) BMS-986315
.
AstraZeneca previously announced positive data from a phase II clinical trial of monalizumab combined with cetuximab in the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)
The antibody drug against NKG2A developed by Huaiyue Biologics is the first in China and the third in the world to be approved to enter the clinic.
It is expected to become the world's best-in-class antibody drug against NKG2A
.
NKG2A complements existing immune checkpoint inhibitor pathways
Studies have found that the inhibitory signal pathway of NKG2A is complementary to the existing immune checkpoint inhibitory pathway, which is mainly reflected in two aspects
.
First of all, NKG2A antibody mainly activates NK cells.
Under this idea, researchers conducted in vitro experiments
.
The results show that the use of NKG2A antibody or PD-L1 antibody alone can improve the activity of immune cells
.
And when the two are used together, it can play a significantly better effect
.
The combined use of NKG2A antibody and PD-L1 antibody can significantly prolong the life of mice (picture from reference 2)
The relationship between KG2A and HLA-E is similar to the relationship between PD-1 and PD-L1, which also makes NKG2A a potential immune checkpoint.
NKG2A inhibitors can promote the anti-tumor ability of T cells and NK cells
.
This is expected to complement existing immunotherapy and better treat cancer patients
.
NKG2A antibody may be another immune checkpoint inhibitor with development potential after PD-1 and CTLA-4 antibodies, which also makes major pharmaceutical companies pay more attention to this target
.
references:
1.
NKG2A, a New Kid on the immune checkpoint block;
2.
Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells;
3.
https:// cancer-at-the-asco20-virtual-scientific-program/?keywords=Innate+Pharma.