Reverse use of immune anticancer therapy to treat autoimmune disease?

[헬스코리아뉴스 / 이충만] A new autoimmune disease treatment has been proposed that uses reverse immuno-oncology, which has been established as a next-generation anti-cancer drug. The idea is to treat autoimmune diseases caused by an overactive immune response by activating proteins that suppress the immune system. Expectations for commercialization are increasing as it enters phase 2 of the clinical trial, but voices of criticism are also pointing to the dangers of this mechanical approach.

When the body is infected with bacteria or viruses, the immune system, such as T cells, is activated. Fever due to an inflammatory reaction is also a phenomenon caused by immune action. However, since excessive inflammatory reactions cause autoimmune diseases, excessive immune responses must be controlled by proteins (CTLA-4, PD-1) that inhibit T-cell function, known as immune checkpoints.

Cancer cells selectively act on immune checkpoint receptors to block the immune system’s attack. At this stage, immune checkpoint inhibitors stop the mechanism by which cancer cells evade the immune system, allowing T cells to attack cancer cells.

Immune checkpoint inhibitors are a method of regulating the current immune response, so the effect of the treatment lasts for a long time, and it has become a standard anti-cancer therapy as it shows a wide range of therapeutic effects regardless of r type of cancer. However, some pharmaceutical companies are trying to develop new autoimmune disease treatments that have turned the current theory of the immune checkpoint 180 degrees.

As immune checkpoint proteins regulate excessive immune responses, the goal is to develop immune checkpoint agents to induce the activity of these proteins and treat autoimmune diseases. In particular, it is expected to provide a new option for autoimmune diseases that are refractory to existing biological agents.

Recently, as several studies have shown the possibility of treating autoimmune diseases by activating immune checkpoint proteins, pharmaceutical companies have jumped into the development of immune checkpoint agents. The leading company is Eli Lilly and Company.

On the 22nd (local time), the company announced that its immune checkpoint agent ‘perezolimab’ had positive results in a phase 2 clinical trial for rheumatoid arthritis through the New England Journal of Medicine (NEJM), a medical journal said to have ensured

‘Peresolimab’ is a humanized immunoglobulin G1 monoclonal antibody that induces the activity of PD-1, an immune checkpoint protein. Lilly anticipates that the selective combination of ‘perezolimab’ and the PD-1 protein will stimulate the immune suppression pathway in vivo to restore immune homeostasis.

To test this, Lilly compared 300 mg and 700 mg of ‘perezolimab’ with placebo in patients with mild to moderate rheumatoid arthritis who were not responding to existing biological agents. The trial participants were given the drug for a total of 12 weeks in 4-week increments.

According to the published results, in the DAS28-CRP score, which evaluates rheumatoid arthritis (RA) disease activity based on a 28-point scale, the ‘perezolimab’ administration group, especially the high dose administration group (700mg), improved the score significantly compared to the control group Positive therapeutic efficacy was also observed in the 300 mg group of ‘Peresolimab’.

Lilly’s view is that these results are very encouraging, given the high unmet medical need for rheumatoid arthritis. Rheumatoid arthritis treatment uses steroids, anti-rheumatic drugs, biological agents, etc. However, steroids have side effects such as toxicity, and antirheumatic drugs and biological agents do not respond in some cases.

However, industry experts criticize the potential for cancer cell growth, which is the biggest drawback of immune checkpoint agents. Immune checkpoint agents are therapies that result from the mechanical inhibition of immune checkpoint proteins, and their safety has not yet been proven, such as the possibility of cancer.

As a result, the ruling on the safety of immune checkpoint agents returned to the US Food and Drug Administration (FDA). If the FDA finds a carcinogenic risk in ‘ferezolimab’, expectations for immune checkpoint proteins in the treatment of autoimmune diseases will be disappointed.

In addition to Lilly, companies developing immune checkpoint agents include US-based Anaptysbio, US-based MSD, and BMS.

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