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For a long time, we have been calling forTumorpersonalized treatment” throughGene sequencingFinding the drivers of tumorsGene mutation, and then use targeted drugs against these driver genes to improve the survival of patients, but these cannot be considered personalized treatments in the strict sense. Because even if tumor patients have the same EGFR or ALK gene mutations, the frequency of these patients' gene mutations, the accompanying passenger gene mutations, the differences in the patients' immune systems, etc., all lead to great differences in the efficacy of the same drug.

So what is personalized treatment?ImmunotherapyThis is not the PD-1 inhibitor that we are all familiar with, but a true analysis of the genetic mutation differences of each tumor patient, and the design of special identification drugs based on these genetic mutations. Recently, scientists at Massachusetts General Hospital have carried out such a project.Clinical trialsI hope this will be helpful to you.

References

Cancer cells in the human body are actually caused by gene mutations. It is because of gene mutations that cancer cells differ from normal cells. These gene mutations will cause some specialantigen(Normal cells do not have), but the human bodyimmunityThe system can detect these differences and kill the cancer cells. Of course, cancer cells can also deceiveImmune cellsInstead of killing them, it is extremely important to try to enhance the immune system's ability to recognize cancer cells.

Researchers at Massachusetts General Hospital evaluated a therapy and conducted a phase 1 clinical trial. This is a clinical study called KEYNOTE-603, and the results of the study were published in Cancer Discovery. This phase of the study evaluated a new personalized tumor neoantigen therapy (INT) called mRNA-4157 (V940). The clinical trial included 16 patients, including 4 patients with non-small cell lung cancer who had undergone surgery and 12 patients with cutaneous melanoma who had undergone surgery.

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The specific process is as follows:The researchers performed comprehensive genomic sequencing of each patient’s tumor tissue to identify the unique genetic mutations that led to the presence of major neoantigens in the patient’s cancer cells, up to 34 of which were then encoded into each mRNA therapy.The use of mRNA therapies and vaccines produces a powerful immune response that is personalized to each patient.cancerTherapy. Why do I say that? Because the drugs infused into each patient are actually designed based on their gene mutation information, which is different from that of other patients.

Ultimately, 12 patients completed the study and 2 patients were lost to follow-up. One patient stopped treatment due to adverse events unrelated to treatment, and one patient died of unknown causes. This personalized medicine mRNA-4157 (V940) is safe and reliable, and the most common adverse reactions include mild fatigue, fever, and tenderness around the injection site. In this study, the personalized medicine mRNA-4157 (V940) was used in combination with the PD-1 inhibitor pembrolizumab to further enhance the immune system's ability to produce a long-term response to cancer. The researchers' analysis of blood tests before and after treatment showed thatmRNA-4157 (V940) can induce multiple forms of immune T cell proliferation. Whether combined with PD-1 or not, mRNA-4157 (V940) can induce activation and proliferation of multiple immune cells.And this induced immune response lasted for 30 weeks after treatment, which means that this therapy has a long-term effect. Based on this research data,The U.S. FDA granted breakthrough therapy designation for mRNA-4157 (V940) combined with PD-1 for the treatment of melanoma.

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If this information is helpful in any way, it is that everyone should remember to keep their genetic testing reports safe, especially when tumor tissue samples are available. Try to get a larger genetic testing package, such as the whole genome, the whole exome, or a large package of 910 genes, to gain a clear understanding of the specific genetic mutations of the tumor. Although targeted drugs may not be found, the design of personalized tumor treatment drugs in the future will definitely require this genetic mutation information. Don't wait until the time comes when tumor tissue samples cannot be used for genetic testing, as that would be quite passive.

Unfortunately, it will take some time for this drug to be released or undergo domestic clinical trials, but perhaps we don’t have to wait too long, as there will be more and more treatments for tumors!

References:

Gainor, JF et al. T Cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination With Pembrolizumab in the Phase 1 KEYNOTE-603 Study, Cancer Discovery (2024).