Research we fund

The University of Texas MD Anderson Cancer Center

To improve the cure rate of patients suffering from acute myeloid leukemia (AML), our study aims to target resistant leukemia stem cells by developing an 'antibody-drug conjugate' (ADC) against CD99, a protein expressed on these cells. Initial tests of two ADC versions have shown promise in combating AML. Our next steps involve refining the anti-CD99 antibody, identifying the optimal drug for conjugation, and testing the ADC on patient-derived leukemia models. Completing these objectives will pave the way for a phase 1 clinical trial, offering a potentially transformative treatment for AML.

Program Name(s)

Translational Research Program

Garvan Institute of Medical Research

Multiple myeloma causes devastating bone disease characterised by focal bone lesions and generalise bone loss, which leads to an increase in bone fractures. Current therapies only stop bones from getting worse so patients continue to suffer fractures. We discovered that inhibiting a molecule called sclerostin in mice increases bone and is much better than current treatments. In this program we will investigate whether inhibiting sclerostin is able to restore lost bone and reduce fractures in patients with myeloma.

Program Name(s)

Translational Research Program

University of California, San Francisco

This project will significantly advance the treatment and prevention of CNS lymphomas in two key areas. One, we will further develop and validate candidate genomic biomarkers that identify high risk disease and that are useful in risk stratification in future clinical investigations in primary CNS lymphoma. Two, we will evaluate novel pharmacologic interventions that we hypothesize will: a) potentiate both the anti-lymphoma immune response, including agonists of the toll like receptor 7 and 8 pathway, as well as the combination of the anti-CD19 monoclonal antibody tafasitamab plus lenalidomide; and b) antagonize the NFkB pathway, via the orally-administered BTK degrader, Nx-5948, that we have demonstrated to be active in preclinical models using patient-derived CNS lymphomas.

Program Name(s)

Translational Research Program

The University of Melbourne

Chimeric antigen receptor (CAR) T cell therapy is a form of immune-based therapy where a patient’s own immune cells are genetically engineered to recognize and kill the tumor cells. This therapy has revolutionized the treatment of certain blood cancers and excitingly, two CAR T cell products were recently approved for the treatment of multiple myeloma. Despite impressive initial clinical data showing responses in 73-98% of patients, most patients still relapse after CAR-T cell therapy within 3 years. Therefore, there is a significant unmet need to further enhance the effectiveness of CAR T cell therapy in this disease. In this project we will investigate whether an approach we have shown to make CAR T cells “fitter” and more effective in solid tumors is also effective in the context of multiple myeloma.

Program Name(s)

Translational Research Program

The University of Melbourne

Chimeric antigen receptor (CAR) T cell therapy is a form of immune-based therapy where a patient’s own immune cells are genetically engineered to recognize and kill the tumor cells. This therapy has revolutionized the treatment of certain blood cancers and excitingly, two CAR T cell products were recently approved for the treatment of multiple myeloma.Despite impressive initial clinical data showing responses in 73-98% of patients, most patients still relapse after CAR-T cell therapy within 3 years. Therefore, there is a significant unmet need to further enhance the effectiveness of CAR T cell therapy in this disease. In this project we will investigate whether an approach we have shown to make CAR T cells “fitter” and more effective in solid tumors is also effective in the context of multiple myeloma.

Program Name(s)

Translational Research Program

The University of Melbourne

Chimeric antigen receptor (CAR) T cell therapy is a form of immune-based therapy where a patient’s own immune cells are genetically engineered to recognize and kill the tumor cells. This therapy has revolutionized the treatment of certain blood cancers and excitingly, two CAR T cell products were recently approved for the treatment of multiple myeloma.Despite impressive initial clinical data showing responses in 73-98% of patients, most patients still relapse after CAR-T cell therapy within 3 years. Therefore, there is a significant unmet need to further enhance the effectiveness of CAR T cell therapy in this disease. In this project we will investigate whether an approach we have shown to make CAR T cells “fitter” and more effective in solid tumors is also effective in the context of multiple myeloma.

Program Name(s)

Translational Research Program

Monash University

As a lymphoma develops it expresses genes that are normally silenced to convey a survival advantage. When these genes are on the X or Y (sex chromosomes) they may present a gender-specific therapeutic target. We have identified a gene (DDX3X in females or DDX3Y in males) that is reactivated in lymphomas such that the lymphomas cannot survive if this gene is removed. This project will develop new ways to inhibit DDX3X and Y as a novel treatment for poor-risk and aggressive lymphoma.

Program Name(s)

Translational Research Program

Universite de Lausanne

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.

Program Name(s)

Translational Research Program

University of Arkansas for Medical Sciences

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.

Program Name(s)

Translational Research Program

MD Anderson Cancer Center

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.

Program Name(s)

Translational Research Program

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.

Program Name(s)

Translational Research Program

Washington University in St. Louis

New treatments for AML and MDS are urgently needed. We have developed and performed preliminary testing of a novel, patent-protected, trispecific NK cell engager named KT1 which targets AML blasts and leukemia stem cells (LSCs) expressing CD33 and CD123 for elimination by effector cells that express CD16a/b. We plan to test the ability of KT1 to release cytokines and facilitate killing of CD33- and/or CD123-expressing targets by different types of CD16a/b-positive effector cell populations including resting natural killer (NK) cells, cytokine-induced memory-like (ML) NK cells, gamma/delta T cells, and macrophages both in vitro and in leukemic mice. We anticipate that a future treatment of AML and/or MDS with KT1 combined with a donor leukocyte transfer of allogeneic NK, ML NK, or gamma/delta T cells will have excellent therapeutic efficacy and a far better safety profile than many currently studied immunotherapies being tested in patients with AML or MDS.

Program Name(s)

Translational Research Program