Novel Method May Identify Melanoma Immunotherapy Targets

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By using a novel approach, researchers were able to identify mutated tumor targets that will enable clinicians to more effectively treat patients with adoptive T-cell therapy, according to data published in Clinical Cancer Research.


One clinical trial showed that, after adoptive T-cell therapy, tumor regression occurred in 72% of patients with metastatic melanoma, although not all patients experienced benefits from the treatment. Steven A. Rosenberg, MD, PhD, of the National Cancer Institute, noted that a lack of clarity regarding the specificity of tumor-infiltrating lymphocytes (TILs).


To determine a better approach for identifying the specificity of TILs, Rosenberg and colleagues sampled tumors from two patients who responded well to adoptive T-cell therapy. They then applied conventional screening—cDNA library screening—to identify non-mutated targets followed by a novel method called tandem minigene library screening to find mutated targets that often go undiscovered with the conventional approach.


The novel method involved next-generation DNA sequencing to sequence the coding regions of DNA from the tumor samples and identifying mutations. The researchers assembled a library of mutations, and rather than synthesize the entire mutated gene, they focused on a small region around the mutation (“minigene”). The minigene library was then scanned to find the targets in the tumors that were recognized by TILs, including two novel mutated targets known as KIF2C and POLA2.


Rosenberg noted that this novel approach will help advance the field of immunotherapy and aid in developing a “new generation” of adoptive T-cell therapy.

Potential Therapy for Rare, Drug-resistant GISTs
Novel Method May Identify Melanoma Immunotherapy Targets

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.

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