Navigation Links
New approach identifies cancer mutations as targets of effective melanoma immunotherapy
Date:6/30/2014

PHILADELPHIA A new approach demonstrated that the recognition of unique cancer mutations appeared to be responsible for complete cancer regressions in two metastatic melanoma patients treated with a type of immunotherapy called adoptive T-cell therapy. This new approach may help develop more effective cancer immunotherapies, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

"This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the major bottlenecks in developing a new generation of adoptive T-cell therapy," said Steven A. Rosenberg, MD, PhD, chief of surgery at the National Cancer Institute (NCI) in Bethesda, Maryland. "The two targets identified in this study play important roles in cancer cell proliferation.

"Immunotherapy has the potential to successfully treat cancer by targeting tumor mutations. We've moved one step closer because of this study," Rosenberg added.

Adoptive T-cell therapy is a type of immunotherapy in which the immune cells infiltrating a patient's tumor, so called tumor-infiltrating lymphocytes (TILs, which are T cells), are harvested, activated and expanded in the laboratory, and transferred back to the patient. Such activated cells are capable of efficiently attacking tumor cells.

"In a clinical trial, up to 72 percent of the patients with metastatic melanoma experienced tumor regression after adoptive T-cell transfer. However, not all patients benefited. This is because the specificity of the TILs remains largely unclear. Our goal was to establish an efficient method to identify the specificity of these cells," explained Rosenberg.

The researchers took tumor samples from two patients who had benefited from the therapy and pursued two screening approaches to identify the tumor targets recognized by the clinically effective T cells. First, they used a conventional screening method called cDNA library screening to identify nonmutated targets. Second, they used a novel method called tandem minigene library screening to identify mutated targets that cannot be found by the conventional method of screening.

For the second approach, the researchers used next-generation DNA sequencing to sequence the coding regions of the DNA from the two patients' tumors, and identified mutations. Next, they generated a library of these mutations. Instead of synthesizing the entire mutated gene, they synthesized only a small region surrounding the mutation (hence the name "minigene" library). They then screened the minigene library to identify those targets in the patients' tumors that were recognized by their TILs.

Using cDNA library screening, the researchers identified three novel nonmutated tumor targets, and four previously known non-mutated tumor targets.

Using tandem minigene library screening, they identified two novel mutated tumor targets, KIF2C and POLA2, which play important roles in cell proliferation.

With the minigene library approach, Rosenberg and colleagues recently reported another novel tumor target recognized by the activated T cells of a patient with bile duct cancer, who responded to adoptive T-cell transfer.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Unique approach needed to accurately assess health of young adult cancer survivors
2. MU receives national award for using mind-body approach to improve health
3. Global, common approach to pharmaceutical supply chain integrity the focus of workshop
4. Editorial calls for comprehensive approach to cancer screening
5. Rutgers team discovers novel approach to stimulate immune cells
6. National initiative launched to change the way biology departments approach undergraduate education
7. A systems approach to preventing obesity in early life
8. Mount Sinai researchers develop a multi-target approach to treating tumors
9. Moffitt researcher, colleagues find success with new immune approach to fighting some cancers
10. A non-antibiotic approach for treating urinary tract infections
11. SingleSource Background Screening Company Calls On Adults To Take Proactive Approach To Stop Child Sexual Abuse
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer ... they remain in the eye of the beholder, according to experts who offered insights ... American Journal of Managed Care. For the full issue, click here . , ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... Lewisville, TX (PRWEB) , ... June 25, 2016 , ... ... in the United States, named Dr. Sesan Ogunleye, as the Medical Director of its ... be the facility Medical Director of our new Mesquite location,” said Dr. James M. ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published June ... with. The article goes on to state that individuals are now more comfortable seeking ... common operations such as calf and cheek reduction. The Los Angeles area medical group, ...
(Date:6/24/2016)... ... ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys are recognized ... this recognition are considered among the top 2 percent of lawyers practicing within the ... this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. Bloom, Burt ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 2016  Collagen Matrix, Inc., ("Collagen Matrix") the ... of collagen and mineral based medical devices for ... Bill Messer has joined the company as ... the growing portfolio of oral surgery, neurosurgery, orthopaedic ... joins the Collagen Matrix executive team as an ...
(Date:6/24/2016)... CAMBRIDGE, Mass. , June 24, 2016 /PRNewswire/ ... the Spaulding Rehabilitation Network,s Dean Center for ... of Physical Medicine and Rehabilitation, MIT Hacking Medicine, ... Center for Innovation, today announced the five finalists ... Hackathon for Lyme disease.  More than 100 scientists, ...
(Date:6/24/2016)... 24, 2016 Research and ... "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" report ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, ... Structural electronics involves electronic and/or electrical components ... replacing dumb structures such as vehicle bodies or ...
Breaking Medicine Technology: