Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive type of peripheral T-cell lymphoma. The majority of patients with AITL are diagnosed at an advanced stage, and have poor prognosis, even with aggressive chemotherapies. Because there has been no improvement in the survival rate of AITL patients over the past two decades ever since the disease was first characterized, there is an urgent need for the discovery and development of an effective treatment. A novel therapeutic target for AITL is the CXCR5-CXCL13 signaling axis, which plays a prominent role in AITL lymphomagenesis, proliferation, and metastasis. By antagonizing CXCR5, Dr. Lolis (PhD, Professor of Pharmacology) and Dr. Foss (MD, Professor of Medicine and of Dermatology) are developing novel therapeutics to treat AITL. They have identified a promising CXCR5 antagonist with decent potency, toxicity profile, and pharmacokinetics for clinical trial in AITL patients. This project is to develop a CXCR5-specific Positron Emission Tomography (PET) imaging probe to explore the pharmacokinetics and pharmacodynamics of the experimental drug. Our research team comprises investigators from Yale PET Center and Yale Cancer Center, and will harness the unique research resources in these centers. Successful completion of this project will set the stage for the clinical trial of the experimental CXCR5 antagonist in AITL patients with the right dose range. Furthermore, as CXCR5 is overexpressed in other types of cancers, i.e., B-cell lymphoma, other T follicular helper cell-mediated lymphomas, prostate cancer, breast cancer, colon cancer, and non-small cell lung carcinoma, the CXCR5 PET imaging probe will also be instrumental in the study of these human diseases.
Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive T-cell lymphoma with poor prognosis. As there has been no improvement ever since this disease was first characterized, there is an urgent need to develop precision therapies for AITL. Based on the fact that CXCR5 has been implicated in AITL at both genetic and protein levels, and proves to be a viable treatment target, we aim to develop a Positron Emission Tomography (PET) imaging assay for accurate diagnosis and screening of AITL patients for clinical trial targeting CXCR5, and to evaluate the pharmacodynamics and therapeutic effects of the experimental drug.
