Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma that specifically targets the central nervous system (CNS), including the brain and spinal cord, or the vitreoretinal space. Alfa Cytology is committed to pioneering new therapeutic approaches for PCNSL treatment for our clients.

Overview of Central Nervous System Lymphoma

The incidence of PCNSL has been steadily increasing, particularly among immunocompromised patients, with a median age at diagnosis of 67 years. The unique pathophysiological mechanisms underlying PCNSL involve specific genetic alterations, including mutations in MYD88 and CD79B, which play crucial roles in the activation of oncogenic signaling pathways. Understanding these mechanisms is vital for the development of targeted therapies.

Fig.1 Primary central nervous system lymphoma high incidence and poor survival. (Puhakka I., et al., 2022)

Therapeutic Development for CNS Lymphoma

Despite the effectiveness of initial treatment regimens, which commonly include methotrexate-based chemotherapy combined with radiation therapy, high rates of relapse remain a significant challenge. This underscores the urgent need for innovative therapeutic strategies aimed at improving patient outcomes. Several promising targeted drugs have been developed and are currently being studied in the hope of finding novel therapeutic strategies to treat this pathology.

Targets	NCT	Therapeutics	Phase
BCR/TLR Pathway	NCT04609046	Rituximab, MTX, lenalidomide, nivolumab
	NCT04481815	Rituximab, MTX ± lenalidomide
	NCT04737889	Rituximab, lenalidomide, MTX, and TMZ
PI3K/mTOR Pathway	NCT02669511	PQR309
	NCT04906096	Paxalisib
	NCT03581942	PI3K Inhibitor Copanlisib with the BTK Inhibitor Ibrutinib

Our Services

At Alfa Cytology, we offer a comprehensive range of services designed to facilitate CNS lymphoma diagnostics and therapy development. Our team provides extensive support throughout the drug development process, from initial screening of compounds to detailed pharmacokinetic and pharmacodynamic studies.

Therapeutics Development

Modeling Services

Preclinical Research

Diagnostic Development

Case Study - Raji Xenograft Model

Model Introduction

The Raji xenograft model serves as a clinically relevant orthotopic platform for studying primary central nervous system lymphoma (PCNSL), an aggressive brain tumor with high initial treatment response but frequent relapse and limited options for recurrent disease. This model recapitulates key histopathological features of human PCNSL, supporting its use in evaluating diverse therapeutic modalities.

Model Information

Model: Raji Xenograft Model
Animal: Nude Mice
Weight: 10-22 g

Cancer Type: Primary Central Nervous System Lymphoma
Age: 8 Weeks
Cell Line: Raji (human Burkitt's lymphoma)

Model Construction

The model was established by stereotaxic implantation of Raji cells (2.0 × 10⁵) into the brains of 8-week-old male BALB/c nu/nu mice. Tumor growth was monitored by survival and histopathological evaluation.

Fig. 2 Workflow of Raji xenograft model establishment. (Source: Alfa Cytology)

In Vivo Efficacy Evaluation

This study employed the established orthotopic PCNSL Raji xenograft model to evaluate the therapeutic efficacy of BNCT.

BNCT with 15-min Neutron Irradiation: BNCT with 15-min neutron irradiation following boron-containing drug administration significantly prolonged median survival compared to untreated controls.
BNCT with 30-min Neutron Irradiation: BNCT with 30-min neutron irradiation following boron-containing drug administration showed a greater therapeutic effect, with significantly prolonged median survival compared to untreated controls. In contrast, boron-containing drug alone or neutron irradiation alone showed no significant therapeutic benefit.

Fig. 3 Survival curves of Raji xenograft models after BNCT treatment. Data are presented as mean ± SEM. (Source: Alfa Cytology)

Contact Us

For more information about our services or to discuss potential collaborations, please reach out to us at Alfa Cytology. Our dedicated team of biological experts is ready to assist you in advancing your research and therapeutic development efforts in CNS lymphoma.

Reference

Puhakka I.; et al. (2022). Primary central nervous system lymphoma high incidence and poor survival in Finnish population-based analysis[J]. BMC Cancer. 22, 236.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.