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Issue link: http://clinicalomics.epubxp.com/i/798822
www.clinicalomics.com March/April 2017 Clinical OMICs 21 the immunotherapeutics field has enjoyed its share of suc- cesses and disappointments . For instance, checkpoint inhib- itor drugs—those that target the various pathways related to T-cell activation, proliferation, and induction of tumor cell death—have been effective in treating melanoma, non- small cell lung cancer (NSCLC), and ovarian cancer . Yet, a significant fraction of patients fail to respond to these ther- apies, which frequently lead to severe complications—a major factor in these therapies often being used as last resort treatments . However, scientists are hopeful that new and ongoing genomic studies will be able to provide insights into better treatment options. The pharmacogenomic efforts could identify specific genetic backgrounds that are sensi- tive to immunotherapy drugs, as similar efforts have for other chemotherapy regimens . "Genomics, mRNA expression analysis, and next-gener- ation sequencing (NGS) in particular have accelerated our understanding of how the immune system can influence the outcome of treatments," explained John Leite, Ph.D., vice president of oncology, market development, and product marketing at Illumina . "It is becoming clearer that a tumor must have the potential to create an immune response com- plete with an arsenal of active immune cells capable of generating an inflammatory response. Moreover, a body of evidence is emerging that demonstrates somatic sequence variants expressed by a broad spectrum of cancers, can pro- vide a means to predict success of certain immune therapies." Fiona Hyland, director of R&D for clinical next generation sequencing at Thermo Fisher Scientific, added that "genom- ics has enabled direct interrogation of the tumor microen- vironment, facilitating the investigation of the types and abundance of cells present and the expression of genes and proteins associated with immune cells and of the tumor." Everything Old Is New Again The immune checkpoint pathways are but one promising area where genomic intervention is starting to shape drug development and usage . For decades scientists have known that due to mutations present within the genome of tumor cells—and not the surrounding normal tissue—cancer cells produce novel sets of antigens that are expressed on their surface . These so-called neoantigens have been attractive drug and vaccine targets for quite some time . However, due (continued on next page) Victor Segura Ibarra and Rita Serda, Ph.D., NCI, NIH Vaccine-Based Immunotherapy from Novel Nanoparticle Systems: Researchers at the Texas Center for Cancer Nanomedicine (TCCN) are creating particle-based vaccines for cancer therapy. The particles carry molecules that stimulate immune cells and cancer antigens (proteins) that direct the immune response. This scanning electron microscope image shows dendritic cells, pseudo-colored in green, interacting with T cells, pseudo-colored in pink. The dendritic cells internalize the particles, process the antigens, and present peptides to T cells to direct immune responses.