On October 12, 2021, Bristol-Myers Squibb announced that the world's first CTLA-4 inhibitor ipilimumab injection was officially launched in China under the trade name: Yiwo.
What is a CTLA-4 inhibitor?
CTLA-4 full name is fully humanized cytotoxic T lymphocyte-associated antigen 4, also known as CD152, is a leukocyte differentiation antigen, is a transmembrane receptor on T lymphocyte , expressed For activated CD4+ and CD8+ T cells. CTLA-4 lowers the immune response by binding to the receptor on the surface of the antigen cell, and terminates the immune response. In other words, CTLA4 is involved in negative immune regulation.
For organ transplant patients, it is necessary to suppress the immune response to prevent organ rejection. Some autoimmune diseases Due to immune disorders, immunosuppressive agents are needed to control the disease. The genetically recombinant CTLA-4 antibody can be effective in vivo and in vitro , Specifically inhibit cellular and humoral immune response.
On the contrary, the treatment of malignant tumors needs to mobilize and increase the body's immune response to kill tumor cells. Therefore, it is necessary to suppress the negative immune regulation of CTLA4 to achieve the effect of negative to positive. Therefore, CTLA-4 inhibitors were developed. By inhibiting CTLA-4 molecules, T cells can proliferate in large numbers and attack tumor cells.
The research and development of CTLA-4 inhibitors is actually earlier than the current hot PD1/PD-L1 inhibitors. However, in the initial study, ipilimumab has a low single-agent efficiency As well as the shortcomings of greater side effects, PD1/PDL1 inhibitors are "come to the top".Follow-up further research found that the unique clinical value of CTLA-4 antibody is reflected in two aspects, sensitization and long-term efficacy.
sensitization is reflected in the ability of CTLA-4 antibody to change the body's immune response, thereby improving the effectiveness of other treatments. That is to say, it belongs to a immunopotentiator . Although its single-drug efficiency is low, it can be used in combination with PD1 /PD-L1 inhibitors. When it is on the right arm, it can get 1+1>2.
's long-term effect is reflected in the ability of CTLA-4 antibody to regulate immune memory cells, which means that it has the function of inducing long-term immune memory and has a long-lasting effect on the activation of the immune system.
Ipilimumab is the first and only CTLA-4 inhibitor approved in China. As early as 2011, Ipilimumab was approved by the US FDA for the treatment of advanced melanoma. In the field of lung cancer, in May 2020, the US FDA approved the combination therapy of nivolumab (O drug) + ipilimumab (Y drug) for sensitive gene mutation negative, PD-L1 ≥ 1% metastasis First-line treatment for patients with non-small cell lung cancer (NSCLC). In the 2021 NCCN guidelines, for the negative gene detection sensitive gene mutations, PD-L1 expression positive advanced non-small cell lung cancer , O+Y dual immunotherapy are included in the level 1 recommendation.
It is worth mentioning:
1. At present, Ipilimumab has just been launched in China, and the price is expensive, but there is a drug donation policy.
2. The currently approved indications in China are: ipilimumab injection combined with PD-1 inhibitor nivolumab injection for non-epithelial unresectable, initial treatment Adult patients with malignant pleural mesothelioma (MPM). The use of other cancers is still a super indication.
3. Since CTLA-4 antibody has a strong and long-lasting ability to activate the immune system, it is more likely to produce immune-related adverse reactions, and it needs to be fully evaluated before use. Immune-related adverse reactions may occur in any organ system,The most common ones are colitis , hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy and endocrine diseases.
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