New approach can help develop more effective immunotherapy for metastatic melanoma -
A new approach has shown that the recognition of the unique cancer mutations appears to be responsible for complete regressions of cancer in both metastatic melanoma patients treated with immunotherapy guy called T cell adoptive 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 main bottlenecks in the development of a new generation of therapy adoptive T cells, "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 an important role in the proliferation of cancer cells.
"Immunotherapy has the ability to successfully treat cancer by targeting tumor mutations. We have moved a step closer because of this study, "said Rosenberg.
Adoptive T cell therapy is a form of immunotherapy in which the immune cells infiltrating the tumor of a patient, so called tumor-infiltrating lymphocytes (TIL which are T cells) are harvested, activated and expanded in the laboratory and transferred to the patient. These activated cells are able to effectively attack tumor cells.
"in a clinical trial, up to 72 percent of patients with metastatic melanoma experienced tumor regression after the transfer of adoptive T cell. However, all patients received. In fact, the specificity of the TIL remains largely uncertain. Our goal was to establish an effective method to identify the specificity of these cells, "said Rosenberg.
The researchers collected tumor samples from two patients who had received therapy and pursued two approaches screening to identify tumor targets recognized by clinically effective T cells. First, they used conventional method of screening called the screening of cDNA libraries to identify non-mutated target. Second, they used a new method called tandem minigene library screening to identify mutated targets that can not be found by the conventional screening method.
for the second approach, the researchers used the new generation of DNA sequencing to sequence the coding regions of DNA from tumors of both patients and the identified mutations. Then, they generated a library of these mutations. instead of the synthesis of all of the mutated gene, they synthesized only a small region surrounding the mutation (hence the name "minigene" library). They then screened the mini-gene library to identify targets in tumors of patients who were recognized by their TIL.
Using the cDNA library screening, the researchers identified three new tumor targets non-mutated, and four previously known non-mutated tumor targets.
Using tandem minigene library screening, they identified two new mutated tumor targets, and KIF2C POLA2, which play an important role in cell proliferation.
With the approach of the library minigene, Rosenberg and colleagues recently reported another novel tumor targets recognized by activated T cells of a patient with cancer of the bile ducts, which responded to adoptive transfer T cell
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