Science: It can target RAS and p53 protein receptors, and the bispecific antibody research has made another breakthrough!

Tumor is a genetic disease that poses a huge threat to human health, and it is also an important issue in the field of disease research.

Tumor is a genetic disease that poses a huge threat to human health, and it is also an important issue in the field of disease research.

Among many oncogenes, the Ras family is a class of proto-oncogenes that encode small GDP binding proteins.

Among the many proteins encoded by tumor suppressor genes, the p53 protein has always been the focus of researchers.

In the field of cancer immunological drug research, RAS and p53 protein are two targets that have not been conquered.

Science Science Immunology (Johns Hopkins University) Bispecific antibody therapy targeting RAS and p53 mutants Bispecific antibody therapy targeting RAS and p53 mutants

Bispecific antibodies are one of the hot spots in the field of drug research and development.

They can recognize tumor cells with RAS gene mutations or TP53 gene mutations, and stimulate T cells to destroy tumor cells with these mutations.

(T cell engager) One end of the bispecific antibody binds to the specific antigen on the surface of the tumor cell, and the other end is capable of activating and binding to the T cell receptor (usually CD3) , thereby recruiting T cells to the vicinity of the tumor cells , Activate them to kill tumor cells (usually CD3)

Schematic diagram of bispecific antibody killing cancer cells by activating T cells

Schematic diagram of bispecific antibody killing cancer cells by activating T cells Schematic diagram of bispecific antibody killing cancer cells by activating T cells

Although RAS and p53 are intracellular proteins, the polypeptide fragments generated after they are degraded in the cell can form a complex with the human leukocyte antigen (HLA) protein and are displayed on the cell surface.

In order to target mutant RAS and p53 protein fragments, the researchers designed bispecific antibodies.

Standard antibodies have two identical arms, but the arms of bispecific antibodies are not exactly the same.

First, the researchers constructed a library of antibody fragments to screen antibodies that can bind to the antigen.

The bispecific antibody H2-scDb targeting the mutant p53-HLA complex significantly reduces tumor volume in a mouse model

The bispecific antibody H2-scDb targeting the mutant p53-HLA complex significantly reduces tumor volume in mouse models.

In the third study led by researcher Suman Paul, the same type of reduced dual-target antibody can also fight a leukemia involving T cells in mice.

Jon Weidanz, an immunologist at the University of Texas at Arlington, said: Although researchers are developing other cancer treatments, these drugs cannot enter the immune system, and as tumors become more resistant, they It is likely to stop working within 1 year.

Bispecific antibodies can condense a wide range of immune responses and have the potential to fight on a larger scale

All in all, by constructing bispecific antibodies that can target receptors and T cells at the same time, the drug can effectively reach the target, and it can still activate the T cell response and destroy cancer cells even when the cell surface expression level is extremely low .

By constructing a bispecific antibody can be simultaneously targeted receptor and T cells, drugs can effectively reach the target, it is still able to activate T cell responses at a very low level of cell surface expression of the situation and eliminate cancer cells by constructing a target capable of simultaneously Bispecific antibodies to receptors and T cells, the drug can effectively reach the target, and it can still activate the T cell response and destroy cancer cells even when the cell surface expression level is extremely low.

Original source:

doi:10.
1126/science.
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doi:10.
1126/science.
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