How dotalizumab (Jemperli) works

Dotalizumab (Jemperli) is an immunotherapy drug whose mechanism of action is based on the principle of immune checkpoint inhibition. It is primarily used to treat ovarian cancers with highly unstable microsatellite mismatches (dMMR) or deficient DNA mismatch repair (dMMR). Before understanding the mechanism of action of dotalizumab, let us first understand the role of immune checkpoints and PD-1 this key molecule.

1.Immune checkpoints andPD-1:

The immune system plays a vital role in protecting the body from infections and abnormal cells. However, in order to prevent the immune system from overly attacking its own tissues, the body also has some self-regulatory mechanisms, one of which involves immune checkpoints. These immune checkpoints are molecules, or receptors, that regulate the magnitude and duration of immune responses.

PD-1 (Programmed Death 1) is a key receptor in immune checkpoints that is usually found on the surface of immune cells, such as T cells (an important immune cell). The main function of PD-1 is to inhibit the activity of T cells to avoid excessive immune response. When PD-1 and its ligand PD-L1 (programmed death receptor ligand 1) or PD-L2 binds, it transmits an inhibitory signal, causing T cells to stop attacking and reduce their activity. This process helps maintain balance in the immune system to prevent autoimmune diseases and excessive inflammatory responses.

2.Mechanism of action of dotilizumab:

Dotalizumab is an anti-PD-1 antibody drug. Its main function is to relieve the resistance of PD-1 to T cells’ inhibitory effect, thereby enhancing the immune system’s attack on cancer cells. Here’s a detailed explanation of the mechanism of action of dotalizumab:

Relieving immunosuppression: In cancer patients, cancer cells are often able to use thePD-1/PD-L1 pathway to evade immune system attack. They overexpress PD-L1, which causes T cells to stagnate around cancer cells and become unable to effectively clear them. The main function of dotalizumab is to bind to the PD-1 receptor and prevent the binding of PD-1 to PD-L1, thereby releasing the inhibition of T cells and allowing them to regain their ability to attack cancer cells.

Activation ofT cells: Dotalizumab reactivates T cells by relieving the inhibitory effect of PD-1 so that it can locate and attack cancer cells. This promotes the aggressiveness of the immune system and increases the intensity of the immune response.

Enhance immune response: The use of dotalizumab increases the ability of T cells to recognize and attack cancer cells, which helps strengthen the immune response. The immune system can clear cancer cells more effectively, slowing the growth and spread of tumors.

Long-lasting anti-cancer effects: Treatment with dotalizumab may result in long-lasting anti-cancer effects. Some patients retain immune memory of the cancer cells after treatment ends, meaning the immune system is still able to recognize and fight the cancer cells' reappearance even after treatment ends.

In short, dotalizumab, as an anti-PD-1 immunotherapy drug, improves the therapeutic effect of ovarian cancer patients by releasing the inhibitory effect of PD-1 on T cells and enhancing the immune system's attack on cancer cells. This mechanism of action represents an innovation in the field of immunotherapy, providing a new treatment option for cancer patients and is expected to improve patients' survival and quality of life. However, specific treatment options should be based on the patient's condition and the advice of a medical professional.

Dotalizumab is not currently on the market in China, and it is not included in medical insurance. Patients cannot purchase it domestically and need to purchase dotalizumab through overseas channels. There are only original drugs available abroad, mainly from the United States, and the price is as high as about 50,000 yuan.