Primary Central Nervous System Lymphoma (PCNSL)
Primary central nervous system lymphoma (PCNSL), also called primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a rare and aggressive form of non-Hodgkin lymphoma that primarily affects the central nervous system (CNS). Unlike other forms of lymphoma that may involve multiple organs, PCNSL is confined to the brain, spinal cord, eyes, or meninges. Our company is at the forefront of PCNSL drug and therapy development services, aiming to improve PCNSL research efficiency and provide innovative solutions to global pharmaceutical companies.
Introduction to PCNSL
Primary central nervous system lymphoma (PCNSL) is an uncommon type of lymphoma that primarily affects the CNS. The incidence of PCNSL ranges from 1-9 cases per 100,000 population. It accounts for approximately 2-5% of all primary brain tumors and is more prevalent among immunocompromised individuals, such as those with HIV/AIDS or organ transplant recipients. B lymphocytes, a type of white blood cell responsible for producing antibodies, accumulate within the CNS and form tumors, leading to the characteristic features of PCNSL.
Pathogenesis of PCNSL
The pathogenesis of PCNSL involves several complex mechanisms that contribute to the development and progression of the disease. One of the key factors is the dysregulation of the immune system, particularly the impairment of immune surveillance within the CNS. This allows the abnormal B cells to evade immune detection and proliferate, leading to tumor formation. Furthermore, activation of the NF-κB pathway is commonly observed in PCNSL, promoting cell survival and resistance to apoptosis.
Fig.1 Therapeutic strategies for PCNSL. (Schaff, Lauren R., et al., 2022)Targets of PCNSL
To develop effective therapies for PCNSL, a thorough comprehension of the intricate molecular targets driving its pathogenesis is imperative. Extensive research has unveiled several pivotal targets within PCNSL, encompassing a diverse array of biological pathways and molecular mechanisms.
- B Cell Receptors (BCRs)
- MYD88
- NF-κB Signaling Pathway
- Angiogenesis Factors
- Immune Checkpoint Pathways
Therapy Development for PCNSL
- Small Molecule Drug
Small molecule drug, particularly high-dose methotrexate (HD-MTX), is the cornerstone of PCNSL therapy at first diagnosis. HD-MTX penetrates the blood-brain barrier and has shown significant efficacy in inducing remission and improving overall survival rates. Studies have demonstrated that HD-MTX-based regimens, in combination with other agents such as cytarabine and rituximab, can achieve high response rates and durable remissions in PCNSL.
- Radioimmunotherapy
Radioimmunotherapy combines the targeting specificity of monoclonal antibodies with the cytotoxic effects of radiation. In this approach, a monoclonal antibody specific to PCNSL cells is labeled with a radioactive isotope. The antibody binds to the tumor cells, delivering localized radiation therapy to the tumor site. This targeted radiation can effectively kill cancer cells while minimizing damage to surrounding healthy tissues.
Our Services
At our company, we are committed to advancing PCNSL diagnostics and therapeutic development services through cutting-edge research and technology platforms. Our expertise lies in the identification and characterization of novel targets, a full suite of preclinical research services, and the development of innovative targeted therapy solutions. Targeted therapies focus on specific molecular markers involved in PCNSL pathogenesis. In line with our company's expertise, we are actively involved in the development of targeted therapies that aim to disrupt the key PCNSL targets.
Platforms of PCNSL Therapy Development
The disease model development platform is another unique feature of our company. With rich experience and a professional team, we provide a variety of model construction services, including cell-based models, organoid models, and animal models, to support the safety evaluation and pharmacokinetic analysis of PCNSL drugs and therapies.
Animal Models of PCNSL
- L735 derived models
- YC8 derived models
- Rev-2-T-6 derived models
- CD4+ T-cell lymphoma derived models
- A20.IIA-GFP derived models
- Raji derived models
- Others
If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Schaff, Lauren R., and Christian Grommes. "Primary central nervous system lymphoma." Blood, The Journal of the American Society of Hematology 140.9 (2022): 971-979.
- Grommes, Christian, and Lisa M. DeAngelis. "Primary CNS lymphoma." Journal of Clinical Oncology 35.21 (2017): 2410.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.