Improve anti-cancer effect and reduce the side effects of immunotherapy!

May 07, 2019 Source: Academic Jingwei

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Cancer immunotherapy is a major breakthrough in the field of cancer treatment in recent years. Because it involves the regulation of the immune system, it is like a double-edged sword, the effect and side effects are equally obvious - although it can effectively attack the cancer cells by the immune system, it will inevitably bring immune response. Related adverse reactions. In order to reduce toxic side effects, doctors often have to reduce the dose of medication. This certainly increases the safety of the treatment, but it also gives some discounts on the efficacy.

Last week, a study published in Nature was expected to provide a solution to this problem. The researchers point out that by inhibiting a protein called TNF, they can "remove" the link between the efficacy and side effects of immunotherapy. In other words, while achieving better results, we can also reduce the side effects of immunotherapy. This is a potential benefit for patients worldwide.

In this study, a class of classical immunocombination therapies consisting of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibody nivolumab. Currently, the US FDA has approved this combination therapy for a variety of cancers including melanoma, renal cell carcinoma, and colorectal cancer. â€œHowever, about 40% of patients have serious side effects,â€ said Professor Ignacio Melero, one of the authors of the study.

â–² The main responsible team of this research. From left to right: Itziar Otano, Pedro Berraondo, Maite Ãlvarez, Ãlvaro Teijeira, Luna Minute, Carmen Ochoa, Ignacio Melero (Source: Cima Universidad de Navarra)

In the face of side effects, patients have to stop the treatment of cancer, or through steroids to relieve symptoms. In patients who are unable to alleviate the side effects of steroids, doctors choose a drug called infliximab that inhibits the TNF pathway and relieves the immune response.

Faced with this phenomenon, the researchers put forward a very creative idea - TNF inhibitors can alleviate the side effects of immune combination therapy. So if you use TNF inhibitors in the early stages of treatment, can you avoid these side effects?

â–² Schematic diagram of the study (Source: Cima Universidad de Navarra)

To answer this question, the researchers used a mouse colitis disease model (colitis is the most common side effect of immunocombination therapy). Preliminary studies have found that in the mouse colitis model, if immunological combination therapy targeting CTLA-4 and PD-1 is used, the symptoms will worsen. This symptom can be alleviated if a TNF inhibitor is used in combination with the treatment. These results indicate that the side effects produced by immunocombination therapy, as well as the relief of side effects by TNF inhibitors, have a similar mechanism of action in mice and humans.

So, do these TNF inhibitors affect the anti-tumor effect of immunoconjugate therapy? In the mouse model, the researchers also did the test. To their surprise, these TNF inhibitors not only do not compromise the anti-cancer effect, but also improve the effectiveness of immunotherapy!

â–² Anti-TNF therapy not only did not reduce the effect of immunocombination therapy, but also prolonged the survival of mice and reduced the tumor volume (Source: References [1])

"We have shown that prophylactic inhibition of TNF during immunotherapy can avoid side effects and improve the effectiveness of treatment in animal models." Professor Pedro Berraondo, another director of the study, said: "This Let us better adjust the dosage of the drug and achieve a stronger anti-tumor effect."

Next, the researchers expect to advance this discovery to clinical trials. If this result can be repeated in patients, it will undoubtedly bring a new treatment paradigm for cancer. We also expect this heavy research to be applied smoothly in the human body, bringing immunotherapy with better efficacy and fewer side effects for patients worldwide.

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