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.
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.
The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out.
The results of this study provide the first appraisal of the diversity of naturally-occurring NY-ESO-1 specific antibodies and could be instrumental in the monitoring of therapy-induced antibody responses in cancer patients receiving NY-ESO-1-based vaccines.
These technologies have aided in the advancement of cancer vaccine development, as illustrated in examples including NY-ESO-1 originally defined by SEREX, and HER2/neu peptides analyzed via high-throughput epitope prediction methods.
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.
Three of the 13 antigens were cancer/testis antigens (MAGEA3, SSX2, and NY-ESO-1), which are expressed exclusively in normal gametogenic tissues and aberrantly expressed in a broad range of cancer types.
To evaluate the potential of two members of this family, MAGE-A4 and NY-ESO-1 antigens, for cancer vaccine in non-small cell lung carcinoma (NSCLC), we examined the expression of these antigens and T cell infiltration in tumor tissue, and evaluated their prognostic significance.
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.
We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule.
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.
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.