Research We Fund

T-cell mediated therapies are all impeded by the same cause- tumoral antigen (Ag) escape: rare Ag– cells in tumors survive the initial attack and lead to relapse. We recently took an innovative approach by enhancing T cells' ability to attack the Ag- cells during the initial treatment. That process is modular by pharmaceutical intervention.

The proposed project will analyze cryopreserved excisional B-NHL biopsies to identify possible pharmaceutical targets potentiating their 'vulnerability’.

Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Most bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Preliminary results suggest that patients with good responses may be able to stop therapy and enjoy a period of time off-therapy with close observation, which may limit long term toxicities caused by continuous therapy. We propose a clinical trial to test this limited-duration approach with recently approved bispecific antibodies for multiple myeloma.

Although many patients with IgM MGUS remain asymptomatic, some of them progress to Waldenstrom Macroglobulinemia (WM) requiring treatment. Recently, we have found that the hereditable alteration of IRF4 gene increases the risk to develop WM, however little is known on the molecular mechanisms responsible for this feature. In this project, we aim to elucidate the role of the germline alteration of IRF4 in promoting WM through oncogenic cooperation with MYD88 and dysregulated immune microenvironment, ultimately paving the way for novel precision therapies for this patient population.

Angioimmunoblastic T-cell lymphoma is a rare, aggressive form of T-cell lymphoma associated with poor clinical outcomes in response to current therapeutic approaches. Recurrent oncogenic mutations in isocitrate dehydrogenase 2 (IDH2) have been identified in patients with angioimmunoblastic T-cell lymphoma and this represents a targetable lesion in other malignancies. However, comprehensive investigations of mutant IDH2 inhibition in angioimmunoblastic T-cell lymphoma are lacking, and this may represent a new therapeutic avenue for a patient population in need of newer treatments