RNA Nanoparticles May Improve Solubility, Delivery and Safety of Cancer Chemotherapy
Two studies led by researchers at the OSUCCC – James suggest that RNA nanoparticles may vastly improve the solubility, delivery and safety of two chemotherapeutic drugs. In one study, researchers used RNA nanoparticles to deliver the chemotherapeutic drug paclitaxel, commonly used to treat breast and many other cancers. That study is published in the journal Nature Communications. The second study used RNA nanoparticles that were engineered in a slightly different way to carry camptothecin in an animal model; the findings are reported in the journal Advanced Science. Both studies were published by Peixuan Guo, PhD, and colleagues in the OSUCCC – James Translational Therapeutics Program. The team established proof-of-concept for RNA nanotechnology more than two decades ago, describing how nano-meter scale RNA structures are assembled and opening a new pathway for research. Read More
Researchers Identify Key Immune Checkpoint Protein That Operates Within T Cells
A study led by researchers at the OSUCCC – James has identified a protein within certain immune cells that is required for optimal immune responses to cancer. The findings, reported in the journal Science Advances, also suggest the protein might be useful for predicting which cancer patients are less likely to respond to immune checkpoint blockade therapy. The protein is PCBP1, or poly(C)-binding protein 1. The researchers found that it helps shape immune responses by ensuring that adequate numbers of activated immune T cells differentiate into cytotoxic T cells, which kill cancer cells. At the same time, PCBP1 prevents the development of too many regulatory T cells, which do not kill cancer cells. Zihai Li, MD, PhD, director of the Pelotonia Institute for Immuno-Oncology (PIIO), was principal investigator. Ephraim Abrokwa Ansa-Addo, PhD, also a member of the PIIO, was first author. Read More
Two Clinical Trials Use Low-Dose Radiation to Treat COVID-19 Infections
Previous studies have shown that low-dose, whole-lung radiation in the form of X-rays can effectively treat severe pneumonia with minimal side effects. Two clinical trials are applying a modern version of this concept to test patients who have acute respiratory distress syndrome (ARDS) as a result of COVID-19 infection. In these phase II trials, patients undergo a single treatment of whole-lung radiation to target and reduce pulmonary inflammation associated with COVID-19 infection. The first trial, called PREVENT, is a national study for COVID-19+ pneumonic patients who do not yet require mechanical breathing intervention (ventilator) but are experiencing severe respiratory distress. Arnab Chakravarti, MD, chair of the Department of Radiation Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, is the national principal investigator (PI). The second study, called VENTED, is for patients who are critically ill and on a ventilator. Chakravarti also is PI for this study, which is taking place only at Ohio State. Read More
Clinical Trial Tests Oral Cancer Drug to Fight Respiratory Symptoms of COVID-19
Researchers at the OSUCCC – James and The Ohio State University Wexner Medical Center launched a phase II clinical trial to determine if an oral cancer drug called ibrutinib can also help patients with cancer or other immunocompromised conditions recover from COVID-19. Physicians at the OSUCCC – James will enroll up to 78 patients with cancer or a precancerous condition who have been hospitalized as a result of a COVID-19 infection. Patients will be randomized to receive either 14 days of standard treatment plus the study drug ibrutinib, or standard treatment alone. Jennifer Woyach, MD, co-principal investigator of the study, says preliminary data suggested ibrutinib has the potential to reduce rates of respiratory failure and death in COVID-19-infected patients. Read More
Blocking Fat Storage May Offer New Way to Treat Lethal Brain Cancer
Glioblastoma (GBM) is a lethal brain cancer that accumulates fats in lipid droplets and uses them as energy for rapid cell division. Blocking an enzyme that GBM cells use to form the lipid droplets might offer a way to treat this disease, according to a study led by principal investigator Deliang Guo, PhD, professor in the Department of Radiation Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. In earlier work, this research team learned that GBM cells accumulate unusually high levels of fatty acids and use them as an energy source for rapid cell growth. Normally, excessive levels of fatty acids are deadly to cells. In this study, published in the journal Cell Metabolism, researchers looked at an enzyme called DGAT1 that GBM cells use to package fatty acids into lipid droplets. Read More
Single Drop of Blood Could Help Rapidly Detect Radiation Sickness
A proof-of-concept study reported evidence that a new testing method has the potential to rapidly identify radiation sickness based on biomarkers measured through a single drop of blood. Scientists at the OSUCCC – James say the test could help save lives through early and real-time identification of the condition to enable timely clinical interventions. “The test uses a drop of blood collected from a finger prick, and results are ready in a few hours. It is rapid, scalable and can serve as a point-of-care-type diagnostic tool for real-time evaluation to screen a large number of individuals in a short time,” says corresponding author Naduparambil Jacob, PhD, associate professor in the Department of Radiation Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Jacob and colleagues reported their findings in the journal Science Translational Medicine. Read More
Study May Refine Predicted Survival Outcomes and Treatment in Younger People With Acute Leukemia
Findings from a retrospective study led by the OSUCCC – James could refine an important set of prognostic and treatment recommendations for younger adult patients with acute myeloid leukemia (AML). The study evaluated molecular characteristics and outcomes of 863 patients with AML who were treated according to 2017 LeukemiaNet (ELN) recommendations. The patients were under age 60 and had a median age of 45 years. ELN recommendations are internationally used for diagnosing and managing people with AML and other leukemias. This study, published in the journal Leukemia, found that 9% of favorable-risk and 53% of intermediate-risk patients should be reclassified as adverse risk, and 4% of favorable-risk and 9% of adverse-risk patients should be reclassified as intermediate risk. If verified, the findings may refine the ELN risk stratification of younger patients with AML. Ann-Kathrin Eisfeld, MD, of the Leukemia Research Program at the OSUCCC – James, was first author. The paper was dedicated to the memory of its senior author, Clara D. Bloomfield, MD, who died during completion of the manuscript. Read More
Preliminary Results of Two Large Immune Therapy Studies Show Promise in Advanced Cervical Cancer
Preliminary results from two independent phase II clinical trials investigating a new PD-1 (programmed cell death protein 1)-based immune therapy for metastatic cervical cancer suggest potential new treatment options for a disease that currently has limited effective options and disproportionately impacts younger women. David O’Malley, MD, director of the Division of Gynecologic Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, presented the results at the European Society for Medical Oncology Virtual Congress in September 2020. O’Malley was the lead presenter for both trials, which were sponsored by Agenus Inc. Each study involved more than 150 patients with recurrent or metastatic cervical cancer from cancer treatment centers across the United States and Europe. All were previously treated with platinum-based chemotherapy as a first-line therapy. The two independent but consecutive phase II trials tested a new immune-based agent called balstilimab given alone or in combination with a second monoclonal antibody drug called zalifrelimab. Read More
Microbiome Could Reveal Whether Immune Therapy Can Benefit a Patient
The intestinal microbiome might offer a window into whether cancer patients can benefit from immune therapy, according to a study by researchers at the OSUCCC – James. Immune therapy using drugs called checkpoint inhibitors has greatly improved survival for many cancer types, but not all patients with those cancers respond to the therapy, and biomarkers are needed to help doctors determine whether the treatment will be effective for a patient. Research has shown that the intestinal microbiome interacts with the immune system, but how that might affect immune checkpoint inhibitor (ICI) therapy is unknown. This retrospective modeling study was designed to help answer that question and to learn if the microbiome can serve as a biomarker for ICI therapy success. Daniel Spakowicz, PhD, of the Molecular Carcinogenesis and Chemoprevention Program at the OSUCCC – James, was first and corresponding author of the study, which was published in the journal BMC Cancer. Read More
OSUCCC – James Physician Leads Team That Performs Life-Saving Surgery on Gorilla
In November 2020, Allan Tsung, MD, director of the Division of Surgical Oncology at Ohio State, led a surgical team that successfully performed an intensive three-hour procedure on an endangered western lowland gorilla named Shaila at the Columbus Zoo & Aquarium. Tsung led a team of 10 medical professionals from the OSUCCC – James, Columbus Zoo & Aquarium, MedVet and OhioHealth Riverside Methodist Hospital. They removed a nearly six-inch liver tumor from Shaila to help reduce the risk of her developing liver cancer. It was a high-risk surgery, but gorilla and human anatomy are similar, so asking for help from a specialist in human liver surgery made sense. Caregivers said Shaila was doing well in her recovery. Read More
National Clinical Trial Led by Ohio State Will Test Efficacy of Immuno-Therapy Plus Radiation in Reducing Endometrial Cancer Recurrence
The OSUCCC – James is leading a multi-institutional phase III clinical trial to determine whether combining targeted immunotherapy with radiation therapy will reduce cancer recurrence in women with high intermediate-risk endometrial (uterine) cancer. The randomized study will compare whether adding a monoclonal antibody called pembrolizumab — a form of immunotherapy — to radiation therapy is more effective than radiation therapy alone in reducing cancer recurrence in patients with newly diagnosed stage I-II endometrial cancer characterized by mismatch repair-deficient tumors. Floor Backes, MD, associate professor in the Division of Gynecologic Oncology at Ohio State and member of the Cancer Control Program at the OSUCCC – James, is national principal investigator. Read More
Rubbery Properties Help RNA Target Tumors Efficiently and Quickly Leave Body
A study by researchers at the OSUCCC – James showed that RNA nanoparticles have elastic and rubbery properties that help explain why these particles target tumors so efficiently and why they possess lower toxicity in animal studies. RNA nanoparticles show great promise for the targeted delivery of anticancer drugs. Understanding their structure and behavior is essential for their possible future use. This study, published in the journal ACS Nano, revealed that, because of their special properties, RNA nanoparticles can stretch and return to their normal shape. These properties could help the particles target tumors by enabling them to slip through the poorly formed walls of tumor blood vessels and enter a tumor mass. Study leader and corresponding author was Peixuan Guo, PhD, professor in the College of Pharmacy at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James. Read More
Study Shows AML Patients Who Participated in Upfront Genomic Testing Had Superior Treatment and Survival Outcomes
Patients with acute myeloid leukemia (AML) who participated in the Leukemia & Lymphoma Society’s (LLS) precision medicine Beat AML® Master Clinical Trial had superior treatment and survival outcomes compared to AML patients who opted for standard chemotherapy treatment, according to findings published in the medical journal Nature Medicine. The Beat AML Master Clinical Trial was launched in 2016 as a collaboration among top leukemia researchers, biopharmaceutical companies and a leading genomics information company aimed at advancing treatment for this disease. In this report, the Beat AML research team presented data demonstrating that genomic analysis of the leukemia cells to identify AML subtypes can be completed within seven days. John C. Byrd, MD, a Distinguished University Professor at Ohio State and co-leader of the Leukemia Research Program at the OSUCCC – James, is lead investigator of the Beat AML trial and corresponding author of the Nature Medicine study. Read More
Therapeutic PD-1 Cancer Vaccine Shown to be Safe and Effective in Preclinical Studies
A study led by researchers at the OSUCCC – James described a potential therapeutic anticancer vaccine that frees suppressed cancer-killing immune cells, enabling them to attack and destroy a tumor. Published in the journal OncoImmunology, the findings showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor vaccine, was safe and effective in a colon cancer syngeneic animal model. The vaccine produced polyclonal antibodies that inhibit the programmed cell death receptor, PD-1, on cancer cells. The vaccine mimics the action of the PD-1 inhibitor nivolumab (marketed as Opdivo), but it avoids triggering the innate and acquired resistance associated with that and related agents, the researchers say. Pravin T.P. Kaumaya, PhD, a professor in the College of Medicine at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James, was first author and vaccine developer. Read More
Study: Young Black Patients With AML Have Worse Treatment Outcomes
Despite advances in treating acute myeloid leukemia (AML), younger Black patients, below the age of 60, with this aggressive blood cancer have a 27% higher chance of dying compared with younger white patients. Bhavana Bhatnagar, DO, and Ann-Kathrin Eisfeld, MD, both of the Leukemia Research Program at the OSUCCC – James, explored factors that might contribute to this disparity and found that, even when Black patients received the same treatment and follow-up care as their white counterparts, they still fared worse. This remained true in Black patients whose cancer carried genetic mutations that typically predict better prognosis and survival. The researchers presented their findings at the Plenary Scientific Session during the virtual 62nd American Society of Hematology (ASH) Annual Meeting. Full findings were published in the journal Cancer Discovery. Read More