Discover new deadly factors against melanoma in mice

Melanoma is a common skin tumor caused by abnormal hyperplasia of melanocytes, which is extremely malignant and accounts for a large part of skin tumor deaths. It occurs mostly on the skin or near the mucous membrane of the skin, as well as in the pia mater and choroid. The incidence rate varies with race, region, and ethnicity. And white people are more likely to develop melanoma than a black person. Sunlight exposure is a risk factor, and the risk factors also include family history, malignant plaque, large congenital melanocyte spasm, and dysplastic sputum syndrome.

Researchers at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins and the Johns Hopkins University School of Medicine reported that two new anticancer agents they have developed appear to boost the immune system's ability to fight melanoma in mice.

The article published in the February issue of Proceedings of the National Academy of Sciences showed that in a mouse model of melanoma, two drugs called s-DAB-IL-2 and s-DAB-IL-2 (V6A) deplete so-called T-regulatory cells when used together. Many T-regulatory cells have a high density of IL2 receptors. Targeted toxin therapy binds to the IL2 receptor, and then the diphtheria toxin portion of the molecule delivers a lethal enzyme to the target cell, causing the cell to die within hours. The reagents for s-DAB-IL-2 and s-DAB-IL-2 (V6A) comprise a regulatory protein called human IL-2 (interleukin-2) which is fused to the chemically modified portion of diphtheria toxin.

This study shows that these proteins show good potential as immunotherapeutic regimens when combined with checkpoint inhibitor therapy, they allow the immune system to develop a stronger, stronger needle that resists tumor reactions, leading to almost Completely knock out the tumor.

Before using proteins for melanoma patients, more animal studies must be conducted, as well as studies on the safety and efficacy of humans.

The new protein used in mouse experiments is a redesigned form of denileukin diftitox (DAB-IL-2), a fusion protein based on diphtheria toxin, used to treat persistent or recurrent cutaneous T-cell lymphoma, an immune Systematic cancer. Researchers have studied that DAB-IL-2 is caused by an interest in diphtheria toxin, which has long been considered an effective biotoxin.

When the drug is put on hold, DAB-IL-2 is considered potential immunotherapy to eliminate T-regulatory cells from patients with advanced malignant melanoma who are no longer able to undergo surgery. Phase 2 clinical studies have shown that it is at least as effective as preventing tumor progression or may be more effective than a single checkpoint inhibitor.

Current research suggests that they believe the drug has a sustained potential as a molecule that can restore the balance of the immune system in the treatment of solid tumors such as melanoma. In their paper, they describe two second-generation forms of the engineered toxin DAB-IL-2: s-DAB-IL-2 and s-DAB-IL-2 (V6A). The V6A form replaces amino acids associated with vascular leak syndrome, resulting in a 50-fold reduction in syndromes in tube studies.

For mouse experiments, the team first injected the animals with conventionals-DAB-IL-2 or V6A forms 7 and 10 days after injection of tumor cells.

Both drugs depleted T-regulated cells in the lymph nodes by 50% and inhibited tumor growth by 75% when evaluated 24 days after the first tumor cell injection. They then tried to use these proteins and then used anti-PD-1 checkpoint inhibitors. A controlled drug, a checkpoint inhibitor, s-DAB-IL-2 or s-DAB-IL-2 (V6A) was treated as sole therapy for mice with melanoma tumors 10 days after tumor initiation.

Other mice were treated with s-DAB-IL-2 or s-DAB-IL-2 (V6A) on days 10 and 13, then treated with anti-PD-1 on days 11, 14 followed by weekly Processed twice.

Anti-PD-1, s-DAB-IL-2, and s-DAB-IL-2 (V6A) have modest effects on tumors when used alone in more advanced tumors, but when administered as a sequential therapy against PD Time-1, s-DAB-IL-2 and s-DAB-IL-2 (V6A) have a so-called "significant" inhibition of tumor growth, showing a 10-fold reduction in tumor size.

Examining tumors removed from mice, the researchers noted that CD8 T cells producing interferon gamma, a significant increase in important anti-tumor effector cells.

In another study, the team has created an alternative form of protein that can remove IL-2 and replace other targeted proteins. Researchers believe that this compound shows some promise in laboratory studies of mouse breast cancer.