Dr. Guo Bingshi of Tianjing Bio: The world's first Claudin 18.2/4-1BB bispecific antibody has entered the clinic, looking forward to the next breakthrough in cancer immunotherapy!

Recently, Tianjing Bio and ABL Bio jointly announced that the bispecific antibody TJ-CD4B (also known as ABL111) that simultaneously targets Claudin 18.

Claudin 18.

▲Dr.

The collision of tight junction proteins and costimulatory molecules

Bispecific antibody therapy is a method of using T cells in the patient's immune system to kill tumors.

Talking about why these two targets were chosen, Dr.

So, how can we develop a safer and more accurate bispecific antibody drug? Tianjing Bio and its partner South Korea ABL Bio have set their sights on two targets that have attracted much attention in recent years-Claudin 18.

Claudin protein is a tight junction (tight junction) molecule, and its function is mainly to adjust the permeability of the barrier structure.

4-1BB, also known as CD137, is an important member of the tumor necrosis factor (TNF) receptor family.

The above-mentioned unique properties of Claudin 18.

Source: 123RF

Next-generation antibodies: a balance of effectiveness and safety

Public information shows that although many therapies targeting Claudin 18.

According to Dr.

The anti-Claudin 18.

The novelty of the 4-1BB antibody used in TJ-CD4B is that it is a third-generation anti-4-1BB antibody with a new and special epitope.

▲Design schematic diagram of TJ-CD4B (Source: Provided by Tianjing Biological)

The therapeutic potential of TJ-CD4B has also been initially verified in preclinical studies.

A few days ago, TJ-CD4B has been approved by the US FDA to carry out a multi-center phase 1 dose-climbing trial to evaluate the safety, tolerability, pharmacokinetics and pharmacokinetics of TJ-CD4B in patients with advanced or metastatic solid tumors.

Bispecific antibodies: the next breakthrough in tumor immunotherapy

Bispecific antibodies have become one of the important research and development directions of Tianjing Biology.
In addition to TJ-CD4B, the company is also developing many bispecific antibodies against other targets, including 4 bispecific antibodies based on PD-L1 monoclonal antibodies to solve patients' resistance to PD-1/PD-L1 There is no response to monoclonal antibody treatment, or the problem of anti-PD-1/PD-L1 monoclonal antibody resistance that is common in the clinical treatment of cancer.

Existing studies believe that tumors that do not respond to PD-1/PD-L1 antibody treatment have immunodeficiencies, such as lack of immune cells that fight tumor cells, or lack of function of immune cells in tumors.
Such tumors are collectively referred to as "cold Tumor".
According to Dr.
Guo Bingshi, Tianjing Bio’s strategy is to develop bispecific antibodies based on anti-PD-L1 monoclonal antibodies.
PD-L1 acts as the main signal and cooperates with other secondary signals.
These signals include 4-1BB antibody and IL.
-7, B7-H3 antibody and CD47 antibody.
This synergy between different signals can transform immunological "cold tumors" into immunologically active "hot tumors" and activate the immune system.
Another bispecific antibody TJ-L14B, which is cooperating with ABL Bio, is to block PD-L1 signal and stimulate 4-1BB signal to activate T cells to produce anti-tumor synergy.
A few days ago, TJ-L14B has completed the first patient administration in the Phase 1 dose-climbing trial in the United States.
This double antibody designed based on the innovative antibody engineering technology platform has also officially entered the clinical research phase.

In addition, Tianjing Biological has also developed an innovative "enhanced" bispecific antibody.
According to reports, the bispecific antibody therapy combines the anti-CD47 monoclonal antibody TJC4 with granulocyte-macrophage colony stimulating factor (GM-CSF) as an "enhanced" CD47 blocker for the treatment of solid tumors.

Regarding the design of bispecific antibodies, Dr.
Guo Bingshi said, “No matter what the target of the bispecific antibody is, it should not be a random combination, but to solve specific scientific and clinical problems and find safety and effectiveness.
This is also the principle that the heavenly creatures have been adhering to.
” In his view, the series of advantages of bispecific antibodies determine that it is very hopeful that it will become the next breakthrough in the field of cancer immunotherapy, bringing more treatment options to cancer patients.