The OSUCCC – James each year awards several Idea Grants to help teams of faculty scientists with innovative ideas for cancer research gather early data that will enable them to apply later for larger grants from the National Cancer Institute (NCI) and other sources. The Idea Grants are funded by the OSUCCC – James Intramural Research Program (IRP), which receives extensive support from Pelotonia and other sources. The grants benefit these research teams by supporting projects in early development that show promise but may not be far enough along to gain large external funding.
Since 2010, the OSUCCC – James has awarded 194 Idea Grants totaling $26.06 million for teams comprising more than 200 investigators across 10 of the 15 colleges at Ohio State, as well as at Nationwide Children’s Hospital and Cincinnati Children’s Hospital Medical Center. These competitive awards provide support for two years and for up to $200,000 each. Of the 194 grants issued, 183 have been funded by Pelotonia for a total of $24.15 million. “Our entire community of Pelotonia participants can be proud of helping fund Idea Grants that advance cancer research,” says OSUCCC Director Raphael E. Pollock, MD, PhD, FACS. “Without this support, some great ideas for combating cancer might not go anywhere.”
The latest round of IRP-funded Idea Grants, awarded last April, consisted of 10 grants totaling $1.76 million. Eight of those received Pelotonia support (totaling $1.36 million), one was supported by the Stefanie Spielman Fund for Breast Cancer Research and one was supported by the Urban and Shelley Meyer Fund for Cancer Research.
Below are summaries of these 10 awards. Each summary contains the project title, the associated team of investigators and the OSUCCC – James research program with which each investigator is affiliated, if applicable. An asterisk beside a name indicates that person is the “contact” principal investigator.
Targeting CD40 for cancer therapy beyond an immune response
Investigators: Xue-Feng Bai, MD, PhD, Translational Therapeutics (TT); Naduparambil Jacob, PhD (TT); Zaibo Li, MD, PhD, Cancer Biology (CB); Junran Zhang, MD* (CB); Xiaoli Zhang, PhD
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, but despite advances in targeted therapies and immunotherapy, it remains the leading cause of cancer-related death worldwide. Because most NSCLC patients who initially respond to therapy eventually develop resistance and relapse, novel treatment strategies are urgently needed. This team’s preliminary data suggest that a protein called cluster of differentiation 40 (CD40), which is important for the immune response through its binding to the ligand CD40L, might also function in the DNA damage response (DDR), outside of its role in the immune response. The scientists also have found that CD40 inhibition slows cancer cell growth and sensitizes NSCLC to inhibitors targeting the DDR kinase ATR and its downstream effector CHK1, which are required for cell survival during replication stress. In this project, they seek to identify previously unrecognized functions of CD40 in DDR and explore its inhibition as a new therapeutic approach against CD40-expressing NSCLC. Since anti-CD40/CD40L drugs and antibodies are already being investigated elsewhere for treating autoimmune disease, this team believes its study results could lead to repurposing existing anti-CD40 drugs for oncology.
Targeting immune inhibitory molecule SUSD2 to rejuvenate CD8+ T-cell antitumor immunity
Investigators: Kai He, MD, PhD (TT); and Haitao Wen, MD, PhD*, Molecular Carcinogenesis and Chemoprevention (MCC)
A key advancement in the treatment of lung cancers is utilizing the immune system to attack cancer cells. However, a majority of lung cancer patients rapidly becomes resistant to immune-based therapeutic approaches. This team has identified a molecule called SUSD2 (sushi domain containing 2) that can cause immune cells to be less functional in killing cancer cells. The researchers hope to demonstrate that inhibiting the SUSD2 molecule can intensify the immune attack against cancer cells and thus improve lung cancer treatment.
Establishing the importance of the CTLH complex in NSCLC
Investigators: Vincenzo Coppola, MD* (CB); and Lianbo Yu, PhD
The fight to cure non-small cell lung cancer (NCCLC) has made progress by using drugs directed at specific genetic alterations (targeted therapy) and by harnessing the patient immunological response (immunotherapy). However, these therapies have limitations in that they can’t be used for all patients and they might have only temporary effects in most patients. This team, which is collaborating in this study with the lab team of David Carbone, MD, PhD, co-leader of the Translational Therapeutics Program, will examine molecules called CTLH proteins that may be excellent targets for novel therapies. When finished, the study could open new avenues of treatment for lung cancer patients who can’t be treated with existing therapies.
Phase II comparative study of anti-pneumococcal vaccine strategy in patients with chronic lymphocytic leukemia
Investigator: Seema Bhat, MD
Patients with chronic lymphocytic leukemia (CLL) have a weaker immune system and are more susceptible to many kinds of infections. One such infection is pneumococcal pneumonia, which is caused by bacteria called Streptococcus pneumoniae. There are two highly effective vaccines against this bug; however, vaccine responses are not as good in patients with CLL as in healthy adults, and the protection from these vaccines may not last long enough. Therefore, Bhat and colleagues are studying a different schedule of administering the vaccine with the hope that it will provide better protection as compared to the currently recommended schedule.
CD74 CAR T-cell therapy in mantle cell lymphoma
Investigators: Lapo Alinari, MD, PhD*, Leukemia Research (LR); Wing Chan, PhD*; Natarajan Muthusamy, DVM, PhD (LR); Yiping Yang, MD, PhD (LR); Xiaoli Zhang, PhD, MS
Mantle cell lymphoma (MCL) is an aggressive and incurable blood cancer. Despite the initial benefit from chemo-immunotherapy, most MCL patients eventually relapse and succumb to their disease. CD74, a protein expressed on the MCL cell surface, mediates a pro-survival signal and drives tumor cell growth. In this project, investigators aim to develop a cell-therapy-based approach using MCL patients’ own normal (autologous) T cells engineered to bind to CD74 [chimeric antigen receptor (CAR) T cells] and efficiently kill MCL cells. The study will provide data for future studies toward developing an effective therapy for patients with MCL.
Project Limb Rescue: A pilot study evaluating the feasibility of transcutaneous sensors for the detection of cancer-related lymphedema
Investigator: Carlo Contreras, MD* (TT); Lynne Brophy, MSN, RN-BC, APRN-CNS, AOCN; Emre Ertin, PhD
Millions of cancer survivors have lymphedema, which is long-term arm swelling, after completing their cancer therapy. For many patients lymphedema is painful, unsightly and debilitating. The early signs of lymphedema are subtle, and sometimes it’s diagnosed only by hospital equipment. This study will use new adhesive-based sensors to detect lymphedema and will develop this method into a way for patients to check for the condition at home. Contreras and colleagues will use their sensors to make measurements in 70 subjects. The team also will use software that it is developing to evaluate a few commercially available devices to detect lymphedema.
Identification of molecular treatment response predictors and associated genomic response patterns in AML patients with IDH mutations
Investigators: Ann-Kathrin Eisfeld, MD (LR); Alice Mims, MD* (LR)
Acute myeloid leukemia (AML) is an aggressive blood cancer; only about 25% of patients are cured despite modern therapies. In recent years scientists have found that the cancer cells of AML patients respond differently to treatment based on differences in the molecular underpinnings of the cells. This project will focus on a subtype of AML patients whose leukemia cells harbor mutations in the isocitrate dehydrogenase (IDH) genes (some 20% of all AML patients). Based on a cohort of 840 patients collected from several cancer centers in the United States, the investigators will determine which treatments work best for patients based on additional gene mutations present in their leukemic cells. The scientists then will design a clinical trial tailored to AML patients with IDH mutations. In this trial, they will track the cancer cells from the time of diagnosis through chemotherapy and compare how the molecular underpinnings change when exposed to different treatments. They hope this work will enable them to provide optimal therapy to each patient based on the genes that are driving the patient’s leukemia.
Development of a risk-assessment tool to identify triple-negative breast cancer patients at risk of rapid relapse
Investigators: Barbara Andersen, PhD (CC); Samila Obeng-Gyasi, MD, MPH* (CC); Saurabh Arun Rahurkar, PhD; Daniel Stover, MD (TT)
Triple-negative breast cancer (TNBC) has worse outcomes than other breast cancer subtypes. A subset of TNBC is characterized by rapid relapse—defined as recurrence and/or death within 24 months of diagnosis. Investigators in this study will create a risk-assessment tool that will identify TNBC patients at risk for rapid relapse. The scientists also will pilot an intervention that addresses psychosocial drivers of rapid relapse. Their goal is to improve clinical outcomes among TNBC patients and leverage study results to increase health equity for patients with aggressive breast cancer. NOTE: The above study is funded by the Stefanie Spielman Fund for Breast Cancer Research at the OSUCCC – James.
The pulmonary effects of standardized research electronic cigarettes: Protonated nicotine effects
Investigators: Peter Shields, MD (CC); Min-Ae Song, PhD* (CC)
The long-term health effects of electronic cigarettes (EC) remain unknown. The most popular EC devices on the market predominantly contain nicotine salts that make them much less irritating and much less harsh to inhale but could lead to much higher nicotine content. This study will evaluate the lung toxicity of EC by switching from cigarettes to EC with and without nicotine. This data is critical to inform policies across the United States for reducing the amount of nicotine in EC with the intent of reducing addictiveness and toxicity.
NOTE: The above study is funded by the Urban and Shelley Meyer Fund for Cancer Research.