Research We Fund

In the Cancer Immunology field, the “aging” variable has not been investigated profoundly yet, even though aging is the first factor associated to cancer. This represents a major limitation on the significance of the experimental results and their translation to the clinic. We believe that with our proposal we can shade light on important biological processes which drive immunotherapy failure. We have shown that T cell function is dependent not only on the differentiation state but also on their biological age. Thus, taking in consideration aging and the age-driven metabolic defects in T cells will help to better understand their biology and develop better strategies to boost immunotherapy.

We have observed that non-glycosylated CST6 proteins suppress osteoclast differentiation and function without causing immunosuppression. We aim to determine whether BCMA-CAR-T cells which are engineered to secret CST6 proteins kill myeloma cells and suppress bone lytic lesions without immune suppressive effects in myeloma. Our ultimate goal is to develop a CAR-T-cell based immune therapy to prevent bone loss and disease progression in myeloma patients.

TP53-Y220C is a recurrent hotspot TP53 mutation observed predominantly in AML and MDS among hematological malignancies. This study aims to investigate the mechanism of action and therapeutic activity of PC14586, a compound designed to bind p53-Y220C protein and stabilize it in the wild-type conformation and to develop mechanism-based combinations that improve its efficacy in TP53-Y220C mutant AML.

Follicular lymphoma is a common form of blood cancer, affecting 15,000 new patients annually in the United States, but it remains incurable with conventional treatments. Bispecific antibodies represent a new class of therapies that engage the immune system to attack lymphoma cells and have shown promising effectiveness in inducing remissions in patients with this disease, but even they are unlikely to be curative. Researchers from the Dana-Farber Cancer Institute here propose to analyze lymphoma cells from patients undergoing treatment with bispecific antibodies on several complementary clinical trials to determine how these cells evade the immune system and develop resistance. It is believed that such mechanisms of resistance may reveal vulnerabilities within the lymphoma cells that novel treatments can overcome in combination with bispecific antibodies to cure patients with follicular lymphoma.