Navigation Links
Going viral to target tumors
Date:3/5/2014

March 5, 2014, New York, NY A Ludwig Cancer Research study suggests that the clinical efficacy of checkpoint blockade, a powerful new strategy to harness the immune response to treat cancers, might be dramatically improved if combined with oncolytic virotherapy, an investigational intervention that employs viruses to destroy tumors.

Published today in the journal Science Translational Medicine, the study evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected directly into one of two melanoma tumors implanted in mice, followed by an antibody that essentially releases the brakes on the immune response. The researchers report that the combination induced a potent and systemically effective anti-tumor immune response that destroyed the non-infected tumor as well. Even tumor types that have hitherto proved resistant to checkpoint blockade and other immunotherapeutic strategies were susceptible to this combined therapy.

"Many patients have benefited from cancer immunotherapies," says Dmitriy Zamarin, a member of Ludwig's Collaborative Laboratory at Memorial Sloan Kettering Cancer Center (MSK) and lead author of the study together with James Allison of the MD Anderson Cancer Center in Houston, and Jedd Wolchok, Director of the Ludwig Collaborative Laboratory at MSK. "But they have not been effective for all patients, or against all cancer types, since most cancers can potently suppress immune responses. We want to extend the benefits of immunotherapies to more patients and optimize their use against a larger variety of cancers."

Zamarin and his colleagues found that an inflammatory immune response induced in the tumor by NDV primarily accounts for the efficacy of the therapy. The checkpoint blockade antibody used in this study binds CTLA-4, a molecule found on immune cells that acts like a brake (or "checkpoint") on the immune response. A version of this antibody is already used for cancer therapy, and it has proved potent in a clinical trial evaluating its combination with another immunotherapy as well.

The researchers noticed that when NDV was injected into a tumor implanted in mice, cancer-killing immune cells flooded into that tumor. "But we also found, to our surprise, that a similar infiltration of activated immune cells occurred in a distant tumor, one in which the virus was never detected," says Zamarin.

The researchers show that NDV infection alerts T cells of the immune system to the presence of cancer cells, which otherwise suppress immune surveillance and attack. Subsequent injection of the anti-CTLA-4 antibody dials up the incipient anti-tumor response so dramatically that it overcomes the tumor's immune suppression and destroys both NDV-exposed tumors and unexposed tumors. And the effect appears to be durable. When the same tumors are reintroduced into treated animals, they are swiftly eliminated.

Combining the two therapeutic strategies, Zamarin explains, overcomes the limitations of each. Oncolytic virotherapy has long been hindered by the immune system's tendency to disable systemically introduced viruses long before they can target tumors. The current study circumvented this problem by injecting NDV directly into the tumor.

Checkpoint blockade, meanwhile, has failed against tumors that suppress immune detection and attack. The researchers found that NDV prompted the cells of such tumors to betray themselves to the immune system when they informed it about the virus. As a consequence, the strategy even made colorectal and prostate tumors that were resistant to immunotherapy susceptible to checkpoint blockade.

The team also found that NDV could be used to boost the effects of an investigational immunotherapy known as adoptive T cell transfer, in which T cells are taken from patients, trained to recognize specific tumors and then reintroduced into their bodies. Adoptive transfer too has been hampered by the ability of tumors to suppress immune responses.

Pretreatment with NDV may similarly boost other immunotherapies. Additionally, Zamarin notes, NDV could be engineered to package and express immune factors that might further boost desirable elements of the anti-tumor response. The researchers are now working to expand production of NDV and devise protocols to evaluate their combination therapy in early stage clinical trials.


'/>"/>

Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

Related medicine news :

1. Yoga regulates stress hormones and improves quality of life for women with breast cancer undergoing
2. Study: Resilience in parents of children undergoing stem cell transplant
3. Most women undergoing surgery for vulvar cancer maintain healthy body image and sex life
4. Athletes “Toward Injury Prevention in Sports” TIPS Gets Going in Las Vegas
5. Going Back To Fitness Basics for Big Results: CrossFit Hub Releases New and Funky Exercise Clothing for Workouts
6. Las Vegas Fit Body Boot Camp The Lakes to Host Grand Opening Charity Event with Proceeds Going to Local Non-Profit, The First Tee of Southern Nevada
7. Salon Program Is Going on at Uniwigs.com
8. The Radiosurgery Society® Announces Initial Results from Ongoing, Multi-Center SRS/SBRT Patient Registry
9. Life Support Technologies Group Announces That Hyperbaric Medicine Shown to Benefit Breast Cancer Survivors Undergoing Breast Reconstruction
10. The Forbes Living Talk Show Is Going Green
11. oGoing Launches Android App for Small Business Social Media Marketing, Online Networking and Lead Generation
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/20/2017)... , ... February 20, 2017 , ... ... Constellation Brands to purchase a new ultrasound-enhanced thrombolysis machine, a state-of-the-art device that ... gift was facilitated by the Pepin Family Foundation. , “We greatly appreciate this ...
(Date:2/19/2017)... ... February 19, 2017 , ... ... result in better care, and MEDfx and the Delaware Health Information Network (DHIN) ... , As the nation’s first state-wide health information exchange, DHIN stores and shares ...
(Date:2/18/2017)... ... February 17, 2017 , ... Butler Mobility invited Ken Matthews ... and other Butler products. Ken was impressed with the safety and reliability of ... the product on his show. This endorsement by Ken Matthews can be heard ...
(Date:2/18/2017)... ... February 18, 2017 , ... ... the latest information and contact points to easily connect elderly veterans of America's ... living, and elder-care funding. It also conveys material on this year's increase in ...
(Date:2/17/2017)... ... February 17, 2017 , ... Wells ... the electronic prescribing of controlled and non-controlled substances plus the ability to manage ... in the United States now accept electronic prescriptions, according to the Office of ...
Breaking Medicine News(10 mins):
(Date:2/18/2017)... , Feb. 17, 2017 Research and Markets has ... report to their offering. ... The report provides separate comprehensive analytics for the US, ... , Asia-Pacific , Latin America , ... period 2015 through 2022. Also, a six-year historic analysis is provided for ...
(Date:2/17/2017)... , Feb. 17, 2017  Ethicon, Inc. today ... Inc., a privately held medical device company that ... Management System, a novel minimally invasive device for ... Torax Medical will enable Ethicon to offer patients ... laparoscopic Nissen fundoplication surgical procedure. 1 ...
(Date:2/17/2017)... , Feb. 17, 2017 Theravance Biopharma, ... or the "Company") today announced the presentation of ... and orally administered pan-Janus kinase (JAK) inhibitor designed ... Congress of the European Crohn,s and Colitis ... reported further data from its completed Phase 1 ...
Breaking Medicine Technology: