Drug Development for Chronic Lymphocytic Leukemia
While Bruton's tyrosine kinase (BTK) inhibitors have demonstrated remarkable success in treating chronic lymphocytic leukemia (CLL), challenges such as tolerance and drug resistance have emerged. Therefore, there is a critical need for the development of novel therapies and treatment strategies to enhance tolerance, overcome drug resistance, and extend remission periods.
Alfa Cytology is dedicated to providing innovative drug development services for CLL treatment. Our primary focus is on improving CLL outcomes and offering therapeutic strategies for drug resistance. Our comprehensive range of drug development offerings includes BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and immunotherapy drugs. These options aim to address various aspects of CLL treatment and provide diverse therapeutic approaches.
Introduction of Therapies in CLL
CLL predominantly affects older individuals and ranks among the most prevalent forms of leukemia. Thanks to extensive research and advancements in treatment options, novel orally targeted drugs have emerged as the primary choice for frontline CLL therapy. These targeted agents encompass a range of drug classes, including inhibitors of the B cell receptor signaling pathway, inhibitors targeting the anti-apoptotic protein BCL-2, and PI3K inhibitors. Moreover, ongoing clinical trials are investigating an expanding array of new drugs and therapies. These trials hold promise for further enhancing treatment effectiveness and reducing the associated toxicity in CLL.
Fig. 1. Targets of currently approved (black) and investigated (gray) novel agents. (Fürstenau, M. et al., 2019)
Our Services
Development of Inhibitors for CLL
| Drugs | Service Details |
| BTK Inhibitors | Irreversible Inhibitors. Our research and development efforts encompass the design of irreversible inhibitors targeting Bruton's tyrosine kinase (BTK). By strategically designing drug molecules that form covalent bonds with the conserved Cys481 residue in the ATP-binding site of BTK, we aim to create potent and long-lasting inhibitors. Reversible inhibitors. Leveraging our understanding of the SH3 structural domain, we utilize structure-based drug design approaches to develop reversible inhibitors. By designing drug molecules that interact with the SH3 domain through hydrogen bonding or hydrophobic interactions, we aim to modulate the function of the target protein reversibly. |
| BCL-2 Inhibitors | By leveraging our expertise and utilizing computational modeling, molecular docking, and structure-based drug design techniques, we develop inhibitors that possess a high affinity for the BH and BH1-4 domains of BCL-2. |
| PI3K Inhibitors | Based on the results of molecular docking, we conduct a comparative analysis of docking scores and binding modes to screen potential drug candidates that exhibit strong binding affinity to the active site of PI3Kδ and possess potent inhibitory activity against PI3Kδ. To ensure the effectiveness of the developed drugs, we perform cell proliferation assay, kinase assay, and molecular dynamics simulation analysis on the selected drug candidates. |
Development of Therapeutic Antibodies for CLL
| Monoclonal Antibodies | Bispecific Antibodies |
| Our proficiency lies in the development and design of monoclonal antibodies that selectively target specific cell surface markers, including CD20 and CD52. Leveraging cutting-edge techniques, we can generate monoclonal antibodies that precisely recognize these markers, providing precise and targeted therapeutic interventions. | Our capabilities encompass the creation of bispecific antibodies capable of binding to two distinct epitopes simultaneously. Our primary focus is on the development of bispecific antibodies that target CD3 and CD20, facilitating the engagement of immune cells and tumor cells to enhance therapeutic efficacy. |
Development of CAR T-cell Therapies for CLL
We have successfully developed CAR T cell therapy utilizing an established animal model for CLL. Through this approach, we collect T cells and employ genetic modifications to target specific antigens such as CD19 and CD20. The engineered T cells are then reintroduced into the animal model, and their efficacy is thoroughly evaluated through comprehensive testing. This innovative CAR T cell therapy holds great promise for the treatment of CLL and offers a potential breakthrough in improving outcomes.
Development of Combinations Therapies for CLL
We provide combination therapy options that utilize monoclonal antibodies and targeted inhibitors, aiming to enhance the efficacy of CLL treatment. Additionally, we specialize in the development of combination therapies involving different inhibitors, further optimizing treatment outcomes. Our services include testing in animal models of CLL, and facilitating the translation of your research findings into clinical applications.
Advantages of Our Services
- Our team of highly skilled researchers and scientists possesses deep expertise in CLL.
- We specialize in developing targeted therapies specifically designed to combat CLL.
- We have a state-of-the-art antibody discovery platform.
- We excel in evaluating and optimizing drug combinations, leveraging our expertise in targeted agents, and immunomodulators.
Alfa Cytology provides a comprehensive range of services for the pre-development of drugs for the treatment of CLL. With a deep understanding of the complexity of CLL and the urgent need for effective therapies, our team of experienced researchers and scientists is committed to developing novel drugs and treatment strategies to improve outcomes. Contact our committed team for further details or to discuss your unique needs.
Reference
- Fürstenau, M.; et al. Sequential and combination treatments with novel agents in chronic lymphocytic leukemia. Haematologica. 2019, 104(11): 2144.