CD98 protein becomes new target of breaking supportive environment of leukemia cells

Acute myelogenous leukemia (AML) is a kind of strong infective cancer caused by abnormality in the process of bone marrow producing blood cells, and it often shows recurrence and drug resistance. Recently, researchers at the University of California, San Diego (UCSD) found that CD98, a cell surface protein expressed by AML cells, plays a role of promoting cancer, whereas CD98 antibody IGN523 is able to arrest AML cancer cells In vitro and in vivo in mice. The results were published in the recent Cell journal Cancer Cell, which also publishes other studies on recombinant mouse proteins.

"In this study, we demonstrated the critical role of CD98 in promoting the growth of AML cancer cells and found that blocking CD98 is effective in preventing cancer cells from gaining nutrients from the surrounding environment," said Professor Tannishtha Reya, author of the article, "This it is expected to inhibit its proliferation and improve the survival rate of patients."

The authors point out that CD98 itself is involved in the proliferation and regeneration of hematopoietic stem cells in bone marrow. In the case of AML, CD98 seems to have become the "accomplice" of cancer. Experiments show that CD98 is necessary for the survival of AML cancer cells. When it was knocked out, the expression of Bcl2L1 and Akt1, which suppress apoptosis in cancer cells, decreased dramatically, while the expression of Casp1, which promotes apoptosis, was up-regulated. Consistent with this, CD98 expression levels in mouse and human leukemic stem cells (LSCs) were significantly higher than in normal hematopoietic stem cells.

In mouse experiments, the role of CD98 in AML is even more prominent. When CD98 was knocked out, the survival rate of AML model mice suddenly increased to nearly 50%, while the knock-out CD98 "suppression" effect even after AML has occurred is still very obvious. Further analysis revealed a significant reduction in the level of leukemic stem cells in the CD98-knockout mice.

Thus, CD98 is a potential therapeutic target of AML. At present, Igenica Biotherapeutics Company is conducting phase 1 clinical trials of anti-CD98 humanized antibody IGN523, and the indications are recurrent or refractory leukemia. The existing results show that IGN523 showed a good safety and preliminary results. In addition, preclinical studies have shown that IGN523 can be significantly amplified in combination with cytarabine, a chemotherapeutic agent, as well as in non-small cell lung cancer and colorectal cancer mouse models.

The anti-cancer effect of IGN523 was also supported in this study. IGN523 was found to significantly inhibit the proliferation of human AML cancer cells in vitro and their interaction with endothelial cells and reduce their carcinogenic capacity in immunodeficient mice.

On the other hand, Professor Tannishtha Reya's team is particularly interested in the potential of IGN523 in childhood leukemia. "Many of the AML mouse models we use are based on mutations that occur in children with leukemia," she says. "Although many pediatric cancers are currently being treated, childhood leukemia continues to have a high rate of relapse. We plan to collaborate with pediatric cancer experts to test whether CD98 blockers can treat childhood leukemia and whether there will be drug resistance and to enhance the anticancer effects of existing therapies." Flarebio provides you with superior recombinant proteins including recombinant TLR2 at competitive prices.