NY-ESO-1 Based Immunotherapy of Cancer: Current Perspectives

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.

Autoantibody landscape of advanced prostate cancer

“…This is supported by prior studies which suggest that cancer-specific overexpression of non-mutant antigens may comprise the majority of tumor-associated antigens [43][44][45][46] . NY-ESO-1, or cancer testis antigen 1B (CTGAG1B), has been well-characterized as an antigen that elicits humoral immune responses in various cancers including melanoma and breast, lung, bladder, ovarian, and prostate cancers [47][48][49] . Additionally, given its cancer-specific expression pattern outside of the testes [49][50][51][52] , NY-ESO-1 has shown great promise as a potential target for T-cell immunotherapies in various cancers 47 .…”

“…NY-ESO-1, or cancer testis antigen 1B (CTGAG1B), has been well-characterized as an antigen that elicits humoral immune responses in various cancers including melanoma and breast, lung, bladder, ovarian, and prostate cancers [47][48][49] . Additionally, given its cancer-specific expression pattern outside of the testes [49][50][51][52] , NY-ESO-1 has shown great promise as a potential target for T-cell immunotherapies in various cancers 47 . In our unbiased approach to identifying immunogenic antigens, we found that NY-ESO-1 was the top candidate.…”

“…In addition to recovering known and novel epitopes of interest in mCRPC, the findings of the present study highlight potentially conserved B-and T-cell cancer-specific epitopes and a combined B-and T-cell response to cancer. NY-ESO-1 has been found to elicit a high-titer IgG humoral response as well as a cellular immune response in patients with melanoma 47,70 . SART3, or "Squamous cell carcinoma antigen recognized by T-cells 3," was initially discovered as a Tcell epitope and was later found to also stimulate a correlated IgG response 65,67 .…”

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment

“…Studies have shown that tumors possessing these antigens are more likely to induce tolerance and are less responsive to ICB (further explained below) (22,23). In addition, they induce more autoreactivity when targeted by adoptive cell therapy (ACT) (31)(32)(33)(34)(35)(36).…”

“…Peripheral T cells were then engineered to express TCRs against specific tumor neo-antigens in highly mutated tumors such as melanoma and lung cancer (83)(84)(85)(86)(87)(88)(89)(90). Adoptively transferred genetically engineered lymphocytes directed against specific NY-ESO-1 epitopes, a well-known cancer-testis antigen, have shown promising clinical responses across a number of tumors (35). This and other potential TCR targets are currently being investigated, as part of engineered T cell treatments, in clinical trials for lung cancers including NSCLC (NCT03778814) (35).…”