Abstract
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancer-testis antigen (CTAs) with re-expression in numerous cancer types. Its ability to elicit spontaneous humoral and cellular immune responses, together with its restricted expression pattern, have rendered it a good candidate target for cancer immunotherapy. In this review, we provide background information on NY-ESO-1 expression and function in normal and cancerous tissues. Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined. Finally, we describe the immune-based therapeutic options targeting NY-ESO-1 that are currently in clinical trial. We will highlight the recent advancements made in NY-ESO-1 cancer vaccines, adoptive T cell therapy, and combinatorial treatment with checkpoint inhibitors and will discuss the current trends for future NY-ESO-1 based immunotherapy. Cancer treatment has been revolutionized over the last few decades with immunotherapy emerging at the forefront. Immune-based interventions have shown promising results, providing a new treatment avenue for durable clinical responses in various cancer types. The majority of successful immunotherapy studies have been reported in liquid cancers, whereas these approaches have met many challenges in solid cancers. Effective immunotherapy in solid cancers is hampered by the complex, dynamic tumor microenvironment that modulates the extent and phenotype of the antitumor immune response. Furthermore, many solid tumor-associated antigens are not private but can be found in normal somatic tissues, resulting in minor to detrimental off-target toxicities. Therefore, there is an ongoing effort to identify tumor-specific antigens to target using various immune-based modalities. CTAs are considered good candidate targets for immunotherapy as they are characterized by a restricted expression in normal somatic tissues concomitant with a re-expression in solid epithelial cancers. Moreover, several CTAs have been found to induce a spontaneous immune response, NY-ESO-1 being the most immunogenic among the family members. Hence, this review will focus on NY-ESO-1 and discuss the past and current NY-ESO-1 targeted immunotherapeutic strategies.
Highlights
NY-ESO-1 or New York esophageal squamous cell carcinoma 1 is a well-known cancertestis antigen (CTAs) with re-expression in numerous cancer types
NY-ESO-1 expression has been reported in a wide range of tumor types, including neuroblastoma, myeloma, metastatic melanoma, synovial sarcoma, bladder cancer, esophageal cancer, hepatocellular cancer, head and neck cancer, non-small cell lung cancer, ovarian cancer, prostate cancer, and breast cancer [21, 32,33,34,35,36,37,38,39,40,41,42,43,44,45,46]
Cancer vaccines can be targeted toward dendritic cells (DCs) through toll-like receptor (TLR). One example of this approach is the use of a NY-ESO-1 encoding LV305 lentivirus, targeting DCs through TLR3 and TLR7, which induced a strong cellular immune response with significant disease regression in one patient with metastatic, treatment-refractory synovial sarcoma [103]
Summary
The mechanisms underlying the aberrant re-expression of CTAs include DNA demethylation and histone posttranslational modification with recent evidence supporting a role for miRNA-mediated regulation [2, 11] Demethylating agents such as 5-aza-2-deoxycytidine are capable to induce re-expression of certain CTAs in tumor cells but not in normal epithelial cells [12,13,14,15,16]. More recent data points to a role for CTAs in the regulation of epithelial-to-mesenchymal transition as well as tumor cell survival [19] Given their largely restricted expression in adult somatic tissues and their immunogenic potential, CTAs have been considered good candidate targets for cancer immunotherapy.
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