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:5/27/2016)... ... May 27, 2016 , ... Each year ... complementary medicine. Allison Outerbridge is this year’s Life University winner of ... at the university’s Student Leadership Awards ceremony. , Outerbridge is approaching her last ...
(Date:5/26/2016)... ... 26, 2016 , ... W.S. Badger Co. Inc ., the maker of ... When Work Works Award for its use of effective workplace strategies to increase business ... project administered by the Families and Work Institute (FWI) and the Society for Human ...
(Date:5/26/2016)... ... May 26, 2016 , ... Connor Sports, ... as a partner for the Tamika Catchings Legacy Tour that will commemorate ... leader in hardwood basketball surfaces in all forms and levels of the game, Connor ...
(Date:5/26/2016)... ... May 26, 2016 , ... There are nearly 14.5 million ... million cancer survivors worldwide. On Sunday, June 5, 2016, communities around the world will ... Survivors Day®. , National Cancer Survivors Day® is an annual worldwide Celebration of ...
(Date:5/26/2016)... ... May 26, 2016 , ... An April Gallup survey found ... The 550 employees of Sun Health Senior Living (SHSL) may not share ... their doctor and prescription copays for the year, while holding the line on increasing ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... LONDON , May 24, 2016 ... erfüllt beide primären Endpunkte ... und Überlegenheit in ‚ausgezeichneter plus guter ... aufsteigenden Colons    ,      (Logo: ... B.V. gab heute neue positive Daten von der ...
(Date:5/24/2016)... Mass. , May 24, 2016  NxStage Medical, ... technology company focused on advancing renal care, today announced ... plans to participate in the following schedule of investor ... be made available at http://ir.nxstage.com/ . ... Jefferies Healthcare Conference NY, NY           Friday, June ...
(Date:5/24/2016)... HONG KONG , May 24, 2016 /PRNewswire/ ... primer stent de doble terapia del mundo, introduce ... fístula arteriovenosa. OrbusNeich, una compañía global ... cambian las vidas, ha expandido su cartera incluyendo ... catéteres balón JADE™ y Scoreflex™ PTA son los ...
Breaking Medicine Technology: