The expression of New York oesophageal squamous cell carcinoma 1 (NY-ESO-1), one of the most immunogenic cancer-testicular antigens, is largely restricted to cancer and germ cells/placental trophoblasts, with little to no expression in normal adult somatic cells.
With the exploration of specific tumor antigens such as NY-ESO-1, which is expressed in ovarian carcinoma and other malignancies, the development of therapeutic cancer vaccines has been pursued initiating the era of personalized anti-cancer medicine.
T-cell receptor (TCR)-engineered T cells targeting New York esophageal squamous cell carcinoma 1 (NY-ESO-1) have been employed in a number of clinical trials for late stage melanoma, synovial sarcoma, multiple myeloma and other malignancies.
This study in patients with relapsed, refractory, or high-risk multiple myeloma (MM) evaluated the safety and activity of autologous T cells engineered to express an affinity-enhanced T-cell receptor (TCR) that recognizes a peptide shared by cancer antigens New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and L-antigen family member 1 (LAGE-1) and presented by HLA-A*02:01.
NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials.
In this issue, D'Angelo and colleagues confirm the safety and feasibility of adoptive T-cell therapy with autologous T cells engineered to express NY-ESO-1<sup>c259</sup>, an affinity-enhanced T-cell receptor recognizing an HLA-A2-restricted NY-ESO-1-derived peptide, and demonstrate encouraging antitumor responses in 50% of treated patients, particularly in the setting of persistence of polyfunctional NY-ESO-1<sup>c259</sup>-expressing T cells in circulation for at least 6 months.<i>Cancer Discov; 8(8); 914-7.
We employed engineered T cells targeting NY-ESO-1, and the data suggest that robust, self-regenerating pools of CD8<sup>+</sup> NY-ESO-1<sup>c259</sup>T cells produce a continuing supply of effector cells over several months that mediate clinically meaningful antitumor effects despite prolonged exposure to antigen.<i>Cancer Discov; 8(8); 944-57.
Vaccine responses were associated with a detectable population of CD141<sup>Hi</sup> conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in antitumor immune responses.<b>Conclusions:</b> These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively nonimmunogenic myeloid cancer and highlight the potential for induced antigen-directed immunotherapy in a group of patients with limited options.<i>Clin Cancer Res; 24(5); 1019-29.
Furthermore, NY-ESO-1-specific immune responses have been observed in various cancer types; however, their utility as biomarkers are not well determined.
Clinical trials testing broad range of cancer therapeutic vaccines against antigens of MAGEA and NY-ESO-1 families for treating various cancers have shown mixed clinical efficiency, safety and tolerability, suggesting the requirement of in-depth research of CTA expression in normal and cancer stem cells and extensive clinical trials for improving cancer immunotherapy technologies.
Our study demonstrated that the MAGE-A family may be of greater utility than NY-ESO-1 for targeted immunotherapy in a variety of cancer histologies, in particular metastatic melanomas and squamous cell carcinomas.
Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
The observation that the cancer germline (CG) antigen NY-ESO-1 is expressed in 70% to 80% and in approximately 25% of patients with synovial cell sarcoma and melanoma, respectively, prompted us to perform this first-in-man clinical trial using the adoptive transfer of autologous peripheral blood mononuclear cells that were retrovirally transduced with an NY-ESO-1-reactive T-cell receptor (TCR) to heavily pretreated patients bearing these metastatic cancers.
Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.
We illustrated the usage of our platform by monitoring the response of a melanoma patient cohort to an experimental therapeutic NY-ESO-1-based cancer vaccine; inter alia, we found evidence of determinant spreading in individual patients, as well as differential CT antigen expression and epitope usage.
The cancer-testis/cancer-germline antigen NY-ESO-1 is a vaccine target in epithelial ovarian cancer (EOC), but its limited expression is a barrier to vaccine efficacy.
Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK.
Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD19 in B-cell malignancies or a T-cell receptor against NY-ESO-1 in synovial cell sarcoma and melanoma.