Related studies have shown that anti CD38 monoclonal antibody daratumumab can treat severe relapsed / refractory multiple myeloma (MM). This antibody is well tolerated and has high single-agent activity. However, not all patients will respond to the drug, and even some patients eventually have more disease progression. A recent study published in the journal Blood was designed to investigate the effect of CD38 and the level of expression of complement regulatory protein (CIPs) before treatment on the response and whether this protein expression can lead to drug resistance. Recombinant dog proteins are used in the research.
The study included 102 MM patients who had received daratumumab monotherapy (16 mg / kg). The researchers found that at least a majority of patients with response (PR) before treatment had significantly higher levels of CD38 expression in MM cells, while patients who had no PR showed lower levels of CD38 expression. However, the cellular surface expression of CIPs, CD46, CD55 and CD59 was independent to clinical response.
In addition, after injecting daratumumab for the first time, CD38 expression of bone marrow and circulating MM cells decreased; after withdrawal of daratumumab, CD38 expression levels of MM cells rise again. In contrast, only at the time of disease progression, CD55 and CD59 expression of MM cells will increase. All-trans retinoic acid increased the MM cells CD38 levels of patients with resistance to daratumumab and reduced the expression of CD55 and CD59, which makes daratumumab mediated complement-dependent cytotoxicity significantly enhanced.
Together, these data demonstrate that the expression levels of CD38 and CIP can significantly affect daratumumab sensitivity. This reminds us that the next step should be to explore to MM combination therapy strategies which can change the expression levels of CD38 and CIP. For more information about proteins like recombinant App, you can visit Cusabio’s website.
没有评论:
发表评论