Breaking News
December 17, 2017 - Teens Acting Badly? Smog Could Be to Blame
December 17, 2017 - FDA Says ‘Yes’ to Short-Acting Insulin Admelog
December 17, 2017 - Vaping popular among teens; opioid misuse at historic lows
December 17, 2017 - Lower Urinary Symptoms Occur in Almost All Patients with SSc
December 17, 2017 - Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)
December 16, 2017 - Butler Hospital launches international Alzheimer’s disease prevention study
December 16, 2017 - iMedicalApps: Virtual Reality Boosts Self-Confidence for Med Students
December 16, 2017 - Researchers validate five new genes responsible for Amyotrophic Lateral Sclerosis
December 16, 2017 - New genetic analysis of candidiasis reveals surprising fungal sex secrets
December 16, 2017 - New high precision machine-learning model could help accelerate drug discovery
December 16, 2017 - Groundbreaking gene therapy trial brings cure for hemophilia closer
December 16, 2017 - Racial Differences Seen in IgG4 Disease
December 16, 2017 - Treacher Collins Syndrome
December 16, 2017 - New approach to tracking how deadly ‘superbugs’ travel could slow their spread
December 16, 2017 - Muscle paralysis may promote breakdown of bones
December 16, 2017 - WSU scientists create injectable dye to track progression of diseases
December 16, 2017 - Kaiser Permanente delivers clot-busting drugs to stroke patients more than twice as fast as national rates
December 16, 2017 - Some Great Holiday Foods for Weight Loss
December 16, 2017 - Shared Decision-Making Strategies for Lung Ca Screening Get High Marks
December 16, 2017 - Lactic acid bacteria can protect against Influenza A virus, study finds
December 16, 2017 - Cancer immunotherapy’s effectiveness may depend on patient’s genetic makeup
December 16, 2017 - Researchers explore patient-doctor conversations, best practices linked to opioid tapering
December 16, 2017 - ‘Virtual child’ to help professionals learn key techniques to treat children with autism
December 16, 2017 - IU scientists discover way to make drug treatment more successful against malaria
December 16, 2017 - Prostate cancer researchers find significant disparities between two liquid biopsy providers
December 16, 2017 - ED-Diagnosed Lung Ca Patients Worse Off: Clin Onc News Report
December 16, 2017 - Calcium in Urine Test: MedlinePlus Lab Test Information
December 16, 2017 - Pregnancy-related conditions taken together leave moms—and dads—at risk
December 16, 2017 - Research uncovers mechanism implicated in defective function of tumor-associated dendritic cells
December 16, 2017 - OncoBreak: Stubborn Racial Disparities; Paid Medical Leave & Chemo; DIY Gene Tests
December 16, 2017 - Critical link between obesity and diabetes has been identified
December 16, 2017 - Transfusion dependence reduces access to high-quality end-of-life care for leukemia patients
December 16, 2017 - Porvair and Suzhou Tianlong Bio to develop epigenetic analysis technologies
December 16, 2017 - FDA Approves Ixifi (infliximab-qbtx), a Biosimilar to Remicade
December 16, 2017 - Morning Break: Trump to Get Check-Up; Cancerous Transplant; Death Knell for MIPS?
December 16, 2017 - First transcatheter implant for diastolic heart failure successful
December 16, 2017 - ‘Sushi-like’ nanodiscs provide structural snapshots of misfolding proteins
December 16, 2017 - Inherited gene variation may be to blame for poor survival of patients with early-onset breast cancer
December 16, 2017 - Sign-up deadline is Friday, but some people may get extra time
December 16, 2017 - Higher Booze Taxes Might Pay Off for Public Health
December 16, 2017 - Regular Activity in Midlife Spares Joints in Women
December 16, 2017 - Rain May Not Cause Achy Joints After All: MedlinePlus Health News
December 16, 2017 - MedDiet adherence doesn’t affect acute heart failure mortality
December 16, 2017 - HKBU experts develop new generation of smart anti-cancer drug molecules
December 16, 2017 - Chronic Kidney Disease Audit finds wide variations in coding of CKD patients in primary care
December 16, 2017 - Scientists use nanoparticles to fight Mucoviscidosis
December 16, 2017 - Increasing physical activity decreases risk of death from lymphoma
December 16, 2017 - Fear compromises the health, well-being of immigrant families, survey finds
December 16, 2017 - Rejected antibiotic candidate could be worth a second look, research finds
December 16, 2017 - Is Nation on the Right Track to Combat Opioid Crisis?
December 16, 2017 - Arthritis No Longer Just a Disease of the Old: MedlinePlus Health News
December 16, 2017 - Study reveals biology behind why muscle stem cells respond differently to aging or injury
December 16, 2017 - Family members without inherited mutation have increased risk of melanoma
December 16, 2017 - Researchers reveal previously unknown mechanism that inhibits cells’ ability to develop into tumors
December 16, 2017 - Studies highlight potential of fMRI applications to detect, treat epilepsy in children
December 16, 2017 - Active surveillance proposed as first-line approach to manage patients with low-risk PMC of the thyroid
December 16, 2017 - Patients’ life values affect their attendance at medical treatment for pelvic-floor dysfunction
December 16, 2017 - Experts consider hazards of antibiotic resistances to be high
December 16, 2017 - Study finds erectile dysfunction as risk factor for early cardiovascular disease
December 16, 2017 - Amber-tinted glasses may reduce insomnia severity
December 16, 2017 - Arthritis Drug Seen Lowering GvHD Risk
December 16, 2017 - Atoh1, a potential Achilles’ heel of Sonic Hedgehog medulloblastoma
December 15, 2017 - Cornell engineers develop new method to measure vital signs using radio waves
December 15, 2017 - Rutgers studies highlight need for salon clients, workers to protect themselves from health risks
December 15, 2017 - FDA Approves Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
December 15, 2017 - Morning Break: CVS Buying Aetna; Uterus Transplant Baby; Your Brain on Drugs, Redux
December 15, 2017 - Social phobia linked to autism and schizophrenia
December 15, 2017 - Timestrip technology helping to prevent missed vaccinations
December 15, 2017 - Researchers win NIH grants for Alzheimer’s research on Amish resilience and rapid onset
December 15, 2017 - Mitochondrial error-correction mechanism essential for energy production of cells
December 15, 2017 - New report reveals steep rise in lung disease admissions to emergency departments during winter
December 15, 2017 - Study finds social stigma as barrier to successful treatment of children with HIV in Ethiopia
December 15, 2017 - Health Tip: Keep Gift-Giving Stress Under Wraps
December 15, 2017 - Long Stoppage of Bisphosphonates Tied to More Fractures
December 15, 2017 - Triglycerides Test: MedlinePlus Lab Test Information
December 15, 2017 - Study shows interventions, though few, can be effective for students with high-functioning autism
December 15, 2017 - Higher blood sugar during first trimester of pregnancy increases child’s risk of congenital heart defect
December 15, 2017 - Study tests accuracy of laboratory-developed cancer tests and FDA-approved companion diagnostics
December 15, 2017 - Extracellular vesicles can be used to effectively delay progression of kidney damage
December 15, 2017 - Targeted lung cancer treatments may benefit smokers and non-smokers alike
Immune-boosting drug combination may hold promise for treating ovarian cancer

Immune-boosting drug combination may hold promise for treating ovarian cancer

image_pdfDownload PDFimage_print

Johns Hopkins Kimmel Cancer Center researchers demonstrated that mice with ovarian cancer that received drugs to reactivate dormant genes along with other drugs that activate the immune system had a greater reduction of tumor burden and significantly longer survival than those that received any of the drugs alone.

The study already spurred a clinical trial in ovarian cancer patients. The investigators, led by graduate student Meredith Stone, Ph.D.; postdoctoral fellow Kate Chiappinelli, Ph.D.; and senior author Cynthia Zahnow, Ph.D., believe it could lead to a new way to attack ovarian cancer by strengthening the body’s natural immune response against these tumors. It was published in the Dec. 4, 2017, issue of the Proceedings of the National Academy of Sciences.

Ovarian cancer is currently the leading cause of death from gynecological malignancies in the U.S. “We’ve taken two types of therapies that aren’t very effective in ovarian cancer and put them together to make them better at revving up the immune system and attacking the tumor,” says Zahnow, associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.

Zahnow says that a class of immunotherapy drugs known as checkpoint inhibitors, currently being studied at the Bloomberg~Kimmel Institute for Cancer Immunotherapy, helps the immune system recognize cancers and fight them off. The drugs have shown success in treating melanoma, nonsmall cell lung cancer and renal cell cancers, but they have had only modest effects on ovarian cancer.

Similarly, another class of drugs known as epigenetic therapies has been used to treat some types of cancer by turning on genes that have been silenced– either by the presence of chemical tags, known as methyl groups, or by being wound too tightly around protein spools, known as histones–but these drugs haven’t been effective against ovarian cancer either.

Zahnow and her colleagues became inspired to investigate a new way to treat ovarian cancer by two recent publications from their group that showed epigenetic drugs turn on immune signaling in ovarian, breast and colon cancer cells (Li et al., Oncotarget 2014). These immune genes are activated when epigenetic therapy turns on segments of ancient retroviruses that activate type 1 interferon signaling in the cells (Chiappinelli et al., Cell 2015). Stone, Chiappinelli and Zahnow wanted to know if this increase in immune signaling could lead to the recruitment of tumor killing immune cells to the cancer.

Zahnow and her colleagues worked with a mouse model of the disease in which mouse ovarian cancer cells are injected into the animals’ abdomens to mimic human disease. These cells eventually develop into hundreds of small tumors, which cause fluid to collect within the abdomen, a condition known as ascites. Floating in this fluid is a milieu of both cancer and immune cells, offering a convenient way to keep tabs on both the tumor and the animals’ immune response.

The researchers started by pretreating the ovarian cancer cells outside of the animal in a culture dish with a DNA methyltransferase inhibitor (a drug that knocks methyl groups from DNA) called 5-azacytidine (AZA). After injecting these cells into mice, the researchers found that animals receiving the pretreated cells had significantly decreased ascites or tumor burden and significantly more cancer-fighting immune cells in the ascites fluid compared to those injected with untreated cells. These cells also had increased activity in a variety of genes related to immune response. Pretreating these cells with histone deacetylase inhibitors (HDACis), which help DNA uncoil from histones, didn’t affect the animals’ ascites or boost their immune response.

These early findings suggested that changes in gene activity induced by AZA cause the tumor cells themselves to summon immune cells to their location. In addition, when the researchers transplanted untreated cells into mice and treated the animals with both AZA and an HDACi, significantly more immune cells were in the ascites fluid, suggesting that the HDACi was acting on the animals’ immune systems. These mice also had decreased ascites, lower tumor burden and longer survival than mice that received just AZA.

When the researchers treated the mice with both AZA and an HDACi, along with an immune checkpoint inhibitor, they got the greatest response–the highest decreases in ascites and tumor burden, and the longest survival. Further experiments using immunocompromised mice showed that the immune system is pivotal to the action of these drugs, rather than the drugs themselves acting directly to kill tumor cells.

“We think that AZA and the HDACis are bringing the soldiers, or immune cells, to the battle. But the checkpoint inhibitor is giving them the weapons to fight,” says Zahnow, who also collaborated with epigenetics scientist Stephen Baylin, M.D., on this project.

The preclinical data generated through this study is already being used to help patients with ovarian cancer through an ongoing clinical trial to test the effectiveness of combining AZA and a checkpoint inhibitor. Future trials may add an HDACi to determine if it affects outcomes.

“Combining epigenetic therapy and a checkpoint blocker leads to the greatest reduction in tumor burden and increase in survival in our mouse model and may hold the greatest promise for our patients,” says Zahnow.

Source:

https://www.hopkinsmedicine.org/news/media/releases/combination_strategy_could_hold_promise_for_ovarian_cancer

Tagged with:

About author

Related Articles