Entrepreneurial Sciences in Cancer Awardees

2023 Awardees

Ozgur Sahin, Ph.D.

Professor, Department of Biochemistry and Molecular Biology

Project: Lysyl oxidase inhibitors to increase the efficacy of immunotherapy in triple negative breast cancer

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype, primarily treated with chemotherapy. However, resistance to chemotherapy is common, increasing the mortality rates. Immune checkpoint inhibitors (ICIs) have been approved for TNBC patients with refractory disease; however, improvement in survival is limited. Therefore, there is an urgent need for novel therapies to improve immunotherapy efficacy in TNBC and increase patients’ survival. In this project, we will test our newly developed and validated lysyl oxidase (LOX) inhibitors to increase the efficacy of immunotherapy in this deadliest form of breast cancer.

Richard O'Neil, Ph.D.

Assistant Professor, Department of Microbiology and Immunology

Project: Developing point of manufacture RNA transfection and stability during cryopreservation

We have identified an approach for engrafting T cells without the need for prior lymphodepletion that relies on mRNA transfection of cells prior to adoptive transfer. We have identified a key milestone that would significantly enhance the feasibility of deploying this technology clinically: point-of-manufacture processing with mRNA transfection prior to cryopreservation. These studies are designed to identify the most effective RNA preparation and cell preservation methods for transfecting engineered T cell products at manufacturing facilities that are ready to “thaw and administer” directly to patients without further processing at point of care.

2022 Awardees

Philip Howe, Ph.D.

Professor, Department of Biochemistry and Molecular Biology

Project: Small Molecule Inhibitor of ARIH1

Co-Investigators: Breege Howley, Ph.D., and Yuri Peterson, Ph.D.

Dr. Howe's award is funded in part by LOWVELO, MUSC Hollings Cancer Center's fundraising bike ride that channels 100% of rider-raised dollars into cancer research.

Chemotherapy is the standard of care in metastatic triple negative breast cancer (TNBC). Unfortunately, this treatment strategy results in low rates of complete response and the development of recurrent disease. Therefore, there is an urgent need for therapies that can improve TNBC patient outcomes. We have delineated a novel role for ARIH1, an E3 ubiquitin ligase, in tumor progression of TNBC. We found that silencing of ARIH1 in TNBC cells reduces cell invasion and cancer cell stemness that are important for metastasis. Additionally, we and others have shown a role for ARIH1 in chemotherapeutic response. We see increased cell killing in response to the chemotherapeutics paclitaxel and doxorubicin in TNBC cells when ARIH1 is silenced.

To develop an inhibitor of ARIH1 function, we identified small molecules from the South Carolina Compound Collection (SC3) that disrupt ARIH1 activity. Hit compounds from our screen can inhibit ARIH1 function in vitro, phenocopy the inhibitory effects of ARIH1 silencing on cancer stemness and improve chemo-response in TNBC cells. Entrepreneurial Sciences in Cancer funding has allowed us to pursue objectives that are crucial for the preclinical development of our novel therapeutics.

John Wrangle, M.D.

Associate Professor, Department of Medicine

Project: Targeting Tumoral Tissue Factor with a Novel Rationally Designed Bispecific-Antibody Strategy

Co-Investigator: Alessandra Metelli, Ph.D.

Dr. Wrangle's award is funded in part by LOWVELO, MUSC Hollings Cancer Center's fundraising bike ride that channels 100% of rider-raised dollars into cancer research.

Tumors are wounds which do not heal: growing and spreading tumors damage surrounding tissues and attract platelets on their surface. One way that tumor cells attract platelets is by making a protein called Tissue Factor. When platelets are in the tumor they promote tumor growth and spread by feeding cancer cells with growing factors, especially TGFβ. To stop this process, we have designed a two-arm therapy which blocks both Tissue Factor on cancer cells and TGFβ released by platelets.

This therapy is modeled on other drugs for very different targets, but are strategies which have shown promising activity. Unlike previous anti-platelet therapies, this antibody will not stop normal platelet function, so patients are not expected to experience bleeding events. Once we have generated our antibody we propose to study its anti-tumor effect in tumor animal models first, and upon safe and successful results, to test its anti-cancer effects in patients. Based on our unique approach to Tissue Factor antibody design and on our scientific and clinical expertise, we expect our anti-TF/TGFBR2 TRAP antibody to be well-tolerated and to have promising clinical activity potential for cancer patients.