Nanostring Technique Identifies Potential Melanoma Immunotherapy Targets

An advanced "nanostring" DNA expression analysis technique detected seven genes that are potential immunotherapy targets for the treatment of melanoma and could increase the number of patients potentially eligible for adoptive immunotherapy.

Nanostring technology is a variation of the DNA microarray that uses molecular "barcodes" and microscopic imaging to detect and count up to several hundred unique transcripts in one hybridization reaction. Each color-coded barcode is attached to a single target-specific probe corresponding to a gene of interest.

Investigators at the [US] National Cancer Institute (Bethesda, MD, USA) designed a nanostring probe set containing 97 genes, 72 of which were considered potential candidate genes for immunotherapy. Five established melanoma cell lines, 59 resected metastatic melanoma tumors, and 31 normal tissue samples were profiled and analyzed using the nanostring technique.

Results published in the September 10, 2013, online edition of the journal Clinical Cancer Research revealed that of the 72 potential target genes, 33 were overexpressed in more than 20% of studied melanoma tumor samples. Twenty of those genes were identified as differentially expressed between normal tissues and tumor samples. Analysis of normal tissue gene expression identified seven genes with limited normal tissue expression that warranted further consideration as potential immunotherapy target antigens: CSAG2, MAGEA3, MAGEC2, IL13RA2, PRAME, CSPG4, and SOX10. These genes were highly overexpressed on a large percentage of the studied tumor samples, with expression in a limited number of normal tissue samples at much lower levels.

“We identified seven potential candidate genes that deserve further consideration as targets for melanoma immunotherapy,” said senior author Dr. Richard Morgan, a researcher in the tumor immunology section of the [US] National Cancer Institute. “We used nanostring technology because it is very robust, yielding quantitative and extremely reproducible results and, in addition, an antigen expression profile can be constructed for a patient from a very small amount of tumor sample, which makes nanostring a better clinical tool.”

“Our laboratory has developed a battery of different antigen receptors to target a wide range of antigens, and we can engineer human immune cells to recognize the targets in patients’ tumors and kill those cells,” said Dr. Morgan. “This is a good example of how newer technologies like nanostring arm cancer researchers and clinicians with the best gear to make tremendous advancements in cancer research and treatment.”

Related Links:
[US] National Cancer Institute