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Adding EP4 Receptor Agonists to CD20 Antigen Therapy in B-Cell Malignancies

By: Julia Fiederlein
Posted: Friday, April 1, 2022

Previous studies have identified the prostaglandin E2 4 (EP4) receptor as a potential therapeutic target in B-cell leukemia and lymphoma. Thus, Tijana Markovič, MPharm, PhD, of the University of Ljubljana, Slovenia, and colleagues conducted an in vitro/ex vivo study to evaluate the combination of the EP4 receptor agonists PgE1-OH and L-902688 with standard anti-CD20 monoclonal antibody therapy. The results, which were published in the International Journal of Molecular Sciences, unveiled a clinical potential to reduce therapeutic doses and protect patients from drug resistance.

“This work has revealed very important findings leading towards the elucidation of the anticancer potential of PgE1-OH and L-902688, either alone or in combination with monoclonal antibodies,” the investigators commented. “This may contribute to the development of potential therapeutic alternatives for patients with B-cell malignancies.”

In the Burkitt lymphoma–derived Ramos and p53-deficient chronic lymphocytic leukemia (CLL) MEC-1 cell lines, PgE1-OH and L-902688 demonstrated enhanced cytotoxic activity in vitro when administered with the anti-CD20 monoclonal antibodies rituximab, ofatumumab, and obinutuzumab. These enhanced cytotoxic effects were also observed ex vivo in primary B lymphocytes obtained from patients with CLL. In several primary CLL samples, treatment with PgE1-OH and L-902688 did not seem to significantly impact the expression level of CD20. Moreover, PgE-1-OH was found to induce apoptosis and inhibit proliferation in CLL via EP4 receptor triggering.

“As monoclonal antibodies are often used in combination with targeted therapies, we next aim to investigate how the addition of an EP4 receptor agonist complements these combinations,” the investigators remarked. “What is even more important and needs to be addressed in the future is whether EP4 receptor agonists can overcome the resistance of CLL cells to targeted therapy.”

Disclosure: The study authors reported no conflicts of interest.


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