Drug Development for Acute Lymphoblastic Leukemia
Despite significant advancements in new treatments, classical therapies still serve as the cornerstone of ALL treatments. Hence, there is a pressing need to develop novel therapies that demonstrate effectiveness across a wide range of ALL cases. Alfa Cytology specializes in providing drug development services specifically tailored for the treatment of ALL. Our services include the development of various types of drugs, such as targeted therapies and immunotherapies. Our primary objective is to explore innovative therapeutic approaches for ALL, aiming to enhance treatment efficacy and minimize adverse effects in ALL.
Introduction of Treatment for Acute Lymphocytic Leukemia
B-cell lymphocytic leukemia (B-ALL) and T-cell lymphocytic leukemia (T-ALL) are two primary types of ALL. B-ALL constitutes approximately 75% of all ALL cases. Currently, the standard treatment approach for ALL involves a combination of chemotherapy, steroids, and allogeneic stem cell transplantation. However, as researchers delve deeper into understanding ALL, targeted therapies, CAR-T cell therapy, and immunotherapy are emerging as potential treatment options. The development of these new drugs has significantly reduced the dependence on intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation.
Fig. 1. Therapeutic targets in acute lymphoblastic leukemia. (Gavralidis, A.; Brunner, A.M., 2020)
Our Services
Drug Development for B-ALL
- Development of Tyrosine Kinases Inhibitors for B-ALL
Through our phenotypic screening and ligand-focused compound library design, we can discover TKIs that exhibit inhibitory properties against tyrosine kinases. We can optimize existing inhibitors or develop a new generation of TKIs to overcome drug resistance and effectively penetrate the blood-brain barrier.
- Development of Bispecific Antibody for B-ALL
We can help clients design the bispecific T-cell engager, utilizing CD3 as a foundation and incorporating a single-chain variable fragment (scFv) that specifically targets CD19. This development can result in a bispecific antibody capable of binding both CD19-expressing tumor cells and T-cells. Consequently, this antibody facilitates tumor lysis.
- Development of Antibody-Drug Conjugates for B-ALL
We can help you conduct screenings to enhance the efficacy of anti-tumor antibiotics and develop antibodies specifically designed to target B-ALL cells. Additionally, we possess chemical connectors that enable the coupling of these two components.
- Development of CAR T-cell therapy for B-ALL
We develop CAR T cells by introducing the genes of CAR constructs into primary T cells. We develop CAR T cells to specifically target ALL cells by expressing CD19 and CD22 receptors. The CAR T cell therapy we have developed is enhancing the effectiveness and safety of ALL treatments.
Drug Development for T-ALL
- Development Inhibitors for T-ALL
| Drugs | Service Details |
| Proteasome Inhibitor | Based on the role of the 26S proteasome in T-ALL, we develop proteasome inhibitors that selectively inhibit its activity. These targeted designs for proteasome inhibitors have the potential to overcome resistance to chemotherapy. |
| BH3 Mimetics | Our design service for molecular structures of BH3 mimics adopts a strategy of constructing BH3-like compounds. By imitating the action of BH3 proteins, these compounds effectively inhibit the binding of BCL2 to BAX. |
| CDK Inhibitors | Due to the role of CDK4/6 in promoting cell cycle progression at the G1-S phase checkpoint, we specialize in developing CDK4/6 inhibitors that specifically target CDK4/6. Our inhibitors are designed to induce cell cycle arrest and apoptosis in leukemia cells. |
| NOTCH1 Inhibitors | By selectively targeting NOTCH1 signaling, our developed inhibitors disrupt the dysregulated activity of NOTCH1, which plays a critical role in the pathogenesis of T-ALL. Through this targeted approach, we aim to modulate NOTCH signaling and halt the progression of T-ALL, offering potential therapeutic benefits for patients. |
| JAK-STAT Pathway Inhibitors | To develop effective inhibitors targeting the JAK-STAT pathway, we employ high-throughput screening and utilize advanced platforms. Our approach enables us to identify and optimize compounds that specifically inhibit JAK-STAT signaling. |
| mTOR Inhibitors | Given the frequent observation of high PI3K-AKT-mTOR signaling in T-ALL, we specialize in providing development services for mTOR inhibitors. Our services include the development of AKT inhibitors that directly target AKT inhibition, as well as mTOR inhibitors that target both mTORC1 and mTORC2. |
| BET Inhibitors | As BET activity has been linked to aberrant MYC expression, our team focuses on the design and development of BET inhibitors utilizing the structural characteristics of BET proteins. Through our extensive research and development efforts, we develop a range of BET inhibitors that effectively target and inhibit BET activity. By doing so, these inhibitors lead to a significant reduction in MYC expression, ultimately resulting in impaired tumor growth. |
- Development of therapeutic antibodies for T-ALL
Leveraging our antibody design tools and proprietary immunotechnology, we have achieved a remarkable success rate in generating antibodies with exceptional specificity and affinity. In the context of T-ALL, we specifically target CD38, CD52, and IL-7Rα as the key action targets for developing therapeutic antibodies.
In addition, we provide comprehensive Bispecific T Cell Engager (BTCE) development services. Through the utilization of our advanced technology, we design and optimize single-chain variable fragments (scFvs) that target both CD3 and CD38, facilitating cell bridging functions. This innovative approach aims to enhance the efficacy of T-cell engagement and promote targeted killing of T-ALL cells.
- Development of CAR T-cell therapy for T-ALL
We offer a range of strategies to address the limitations associated with CAR T cell therapies for T-ALL. Our services include the development of cell therapies for T-ALL utilizing tumor-specific antigens expressed in malignant T-cells. Additionally, we can develop CAR-modified NK cells to prevent self-killing.
CAR T Cell Manufacturing Process
Advantages of Our Services
- We provide a flexible approach to the design and planning of your drug development program for ALL treatments.
- We aim to accommodate your needs and tailor the program accordingly.
- Our services encompass a broad range of molecules, including monoclonal antibodies, bispecific antibodies, and Fc fusion.
- We possess sophisticated tools for designing antigens that target ALL cells.
- We have extensive experience in developing CAR T cell therapies.
Alfa Cytology is committed to advancing the field of ALL treatment through our comprehensive and tailored drug development services. Partner with us to accelerate the development of innovative therapies and improve outcomes in the fight against Acute Lymphoblastic Leukemia. If you are interested in our services, please feel free to contact us.
Reference
- Gavralidis, A.; Brunner, A.M. Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia. Current Hematologic Malignancy Reports. 2020, 15(4): 294–304.