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Alfa Cytology is dedicated to the field of drug development for leukemia and offers comprehensive, high-quality services to researchers, aiming to discover effective PD-L1 inhibitors for leukemia. Leveraging our professional team and advanced technological platforms, we focus on designing drugs targeting PD-L1 to provide a novel immunotherapy strategy utilizing PD-1/PD-L1 blockade for leukemia therapy.
The interaction between PD-L1, located on the surface of cells, and PD-1, present on the surface of lymphocytes, leads to the inhibition of lymphocyte function and the induction of apoptosis in activated lymphocytes. Research has shown that PD-L1 is overexpressed in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). PD-L1 checkpoint inhibitors have been approved for the therapy of lymphomas and various solid tumors. However, the development of PD-L1 drugs specifically targeting leukemia is still in the trial phase.
Fig. 1. Mechanism of action of PD-1 and PD-L1 inhibitors. (Gong, J. et al., 2018)
Alfa Cytology has focused on PD-L1, an immune checkpoint involved in cancer immune evasion, as one of the targets for leukemia therapy. The types of molecules that have been developed to target PD-L1 that we have supported include monoclonal antibodies and small-molecule inhibitors. Here are the comprehensive services we offer.
| Development of PD-L1 Inhibitors | Development of PD-L1 mAb | Development of PD-L1 Antibody Drug Couplers (ADCs) |
|---|---|---|
| We specialize in the development of novel inhibitors targeting PD-L1, such as small molecules, peptides, or macrocyclic compounds, to address challenges including poor drug permeability, long half-life, and low oral bioavailability. | We provide development services for monoclonal antibodies that block the PD-L1. With the guidance of molecular modeling and protein design expertise, we utilize our therapeutic antibody discovery platform to develop PD-L1 mAbs. | We offer services for the design of ADCs targeting PD-L1, combining ADCs with anti-PD-L1 mAbs to generate bifunctional PD-L1-directed ADCs. |
The development of PD-L1 inhibitors entails the demonstration of their functional properties. We offer a range of validated assays to support their in vitro characterization. Additionally, our services encompass assessing differences between clones or comparing the potency against approved reference products.
PD-L1 Blockade Assay
In the PD-L1 Blockade Assay, we offer two distinct genetically engineered cell lines: effector cells expressing PD-1 and antigen-presenting cells expressing PD-L1. Co-culturing these two cell lines enables the binding of PD-L1 with PD-1, leading to the inhibition of TCR signal transduction in effector cells.
Antibody-dependent Cell-mediated Cytotoxicity (ADCC) Assays
Our ADCC detection services assess PD-L1 mAbs for leukemia drug development. We measure cell cytotoxicity using non-radioactive release assays or flow cytometry with fluorescent dyes, distinguishing target cells from effector cells or viable cells from dead cells.
Antigen-specific T Cell Recall and Activation Assay
Inhibition of the PD-1 pathway has demonstrated the ability to promote the generation of memory T cells, thereby enhancing their anti-tumor efficacy. To investigate this phenomenon, we employ an in vitro antigen recall and activation assay to monitor the formation of memory T cells.
Treg-mediated T Cell Suppression Assay
The balance between effector T cells and Tregs in the tumor microenvironment (TME) has emerged as a significant prognostic factor for patient outcomes and their response to checkpoint inhibitor therapy. We investigate the impact of novel PD-1L inhibitors on Treg functionality through monitoring Treg function assays.
After in vitro characterization, the development of the most promising candidate drugs can be advanced through in vivo models. We offer validated leukemia models, including but not limited to humanized models, xenograft models, and transgenic models. We will assist you in selecting the most suitable model for the development of PD-L1 inhibitors.
We employ a risk-based approach that is efficient and well-organized, ensuring the necessary emphasis on meeting stringent quality standards for your pharmaceutical products. Our experienced toxicology consultants provide invaluable assistance, ensuring effective project implementation through outsourcing or supporting your team.
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Alfa Cytology has been specializing in drug discovery for many years, particularly in the development of PD-L1 checkpoint inhibitors for leukemia. Our PD-L1 inhibitors development services offer a comprehensive approach to drug development, covering various stages from target identification and validation to lead optimization and preclinical testing. This ensures a systematic and effective development process. Please contact us to learn more about how we can assist you in developing anti-PD-1L drugs and leukemia models.
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