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Tyrosine Kinase Inhibitors Target B Lymphocytes

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body's proteins, it leads to various autoimmune disorders. Additionally, when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.

 

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Targeting B cells can, therefore, be a potential treatment for various patient groups. In this study, protein kinase inhibitors that were previously approved to treat ALK-positive lung cancer cells were used to target LTK-positive, actively protein-secreting mature B lymphocytes, including plasma cells. The researchers isolated CD19-positive human B cells from healthy donors and used two alternative methods to stimulate cell maturation towards plasma cells.

Using cell proliferation and flow cytometry assays, the researchers found that ceritinib and entrectinib were effective in eliminating plasma cells from the B cell population. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. This study suggests that certain drugs previously developed to treat ALK-positive malignant cells can be used to target LTK-positive B cells, providing new potential treatment options for autoimmune disorders and blood cancers. Further research is needed to validate these findings and determine the safety and efficacy of these drugs in clinical trials.

Related Products

Cat.No. Product Name Information
S7083 Ceritinib Ceritinib is a potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.

Related Targets

Serine/threonin kinase FLT3 ALK IGF-1R