It is likely to find a way to prevent disease recurrence

In a study published in the journal New England Journal of Medicine, researchers from US and Dutch found mutations of genes related to immune system in metastatic melanoma patients. These patients initially responded to the treatment against PD-1, but the disease relapsed after six months.

Research team from University of California at Los Angeles (UCLA), Jonsson Comprehensive Cancer Center and Netherlands Cancer Institute conducted exon sequencing for the tumor samples of four patients with metastatic melanoma before they received pembrolizumab drug therapy. The researchers also analyzed the protein coding sequence of tumor samples through recombinant mouse proteins after late recurrence. By comparing sequencing results of tumor samples before treatment and after relapse, they found the mutations associated with checkpoint blocking resistance.

The researchers found suspected mutations in three patients. In the body of one of them, they found truncation mutations which affected β-2-microglobulin (B2M) encoding gene. This mutation causes the expression of type I major histocompatibility complex (MHC) molecules, and the molecules can be recognized by CD8T cells immune system. Another two recurrent tumors showed function mutations of gene functions of JAK1 or JAK2 genes, and these two gene encodings interfere related kinases.

First author of the study, doctoral Jesse Zaretsky from Antoni Ribas Laboratory at the University of California at Los Angeles said, "These mutations make the tumor produce resistance to the way of immune system killing tumors. For example, JAK mutations are associated with interferon receptors and make tumors become insensitive to the signals of slowing down tumor growth and killing tumors."

The team established cell lines of recurrent tumor patients with JAK2 function-loss mutations. Making used of nCounter expression system of NanoString Technologies company, they found that JAK2 protein expression deletion after treatment, decrease of interferon-γ activity and protein yield reduction are all associated with antigen presentation and T cell activity. The researchers plan to focus on the study of JAK2 protein using recombinant dog proteins, as JAK2 protein becomes the new key of treating cancer.

Zaretsky said that more large-scale studies are needed to observe whether this kind of mutations identified in patients with recrudescent metastatic melanoma is common in patients receiving other disease checkpoint blocking therapy and to look for other potential resistance-associated mutations. Researchers are now creating cell line models to study the pathogenesis of these resistance mutations, hoping to find a way to prevent disease recurrence. Flarebio provides you with good-quality recombinant proteins including recombinant CDH12 at good prices.