Prolongation of Overall Survival in Advanced Lung Adenocarcinoma Patients with the XAGE1 (GAGED2a) Antibody

Abstract

Purpose: The cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately 40% of advanced lung adenocarcinomas. We investigated the clinical relevance of the XAGE1 (GAGED2a) immune responses in patients with advanced lung adenocarcinoma.Experimental Design: The XAGE1 (GAGED2a) antigen expression and EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody and T-cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated with conventional platinum-based doublet chemotherapy and patients with EGFR-mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy. The overall survival (OS) rates of the antibody-positive and -negative patients were investigated.Results: The results showed that the OS of antibody-positive patients was prolonged significantly compared with that of antibody-negative patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs. 15.6 months, P ¼ 0.05) or EGFRmt (34.7 vs. 11.1 months, P ¼ 0.001) tumors. Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen-positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune activation in the antibodypositive patients.Conclusions: The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for patients with lung adenocarcinoma as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy.

Successful treatment with nivolumab for lung cancer with low expression of PD‐L1 and prominent tumor‐infiltrating B cells and immunoglobulin G

“…Tumor‐infiltrating plasma cells produced the various specific antibodies to cancer‐testis antigens, such as LAGE‐1, the MAGE family, and NY‐ESO‐1 in lung cancer . In advanced lung cancer, the presence of circulating XAGE‐1 antibody to its cancer‐testis antigen indicated favorable survival in association with activating the antigen‐specific T cells . Tumor‐infiltrating plasma cells may be, at least in part, involved in anti‐tumor effects through the production of tumor‐specific antibodies.…”

Lack of XAGE‐1b and NY‐ESO‐1 in metastatic lymph nodes may predict the potential survival of stage III melanoma patients

“…Ohue et al 27 recently reported that the expression of XAGE-1 was associated with poor prognosis and that the presence of anti-XAGE-1 antibody was strongly associated with prolonged OS in patients with advanced lung adenocarcinoma. Ohue et al 27 recently reported that the expression of XAGE-1 was associated with poor prognosis and that the presence of anti-XAGE-1 antibody was strongly associated with prolonged OS in patients with advanced lung adenocarcinoma.…”

“…The NY-ESO-1 + group also tended to have poorer outcomes than the negative group, yet the difference was not significant. In addition to the suggestion that CTA may be ideal targets for tumor-specific immunotherapy because of their tumor-restricted expression patterns, 7 previous studies have also indicated that CTA expression is associated with poorer disease-free survival and/or OS in a variety of cancers, such as melanoma, 25 non-small cell lung cancer, [26][27][28] ovarian cancer, 29 breast cancer, 30 multiple myeloma, 31 colorectal cancer, 32 bladder cancer, 33 prostate carcinoma, 34 vulvar cancer, 35 gastrointestinal stromal tumors, 36 squamous cell carcinoma 37 and stomach cancer. 38 Expression of NY-ESO-1 is reportedly associated with disease progression and poor prognosis in various cancers, including melanoma.…”

Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients

“…Expression of CCR4, NY-ESO-1, and XAGE1 (GAGED2a) was examined by IHC as described previously (11,(19)(20)(21)(22).…”

“…The data were analyzed using FlowJo software (version 7.6.5; Tree Star). A number of TNFa-staining cells stimulated with XAGE1 (GAGED2a) OLPs that was more than 2-fold the number of staining cells stimulated with HIV gag control peptides (a mixture of MGARASVLSGGELDR and ASVLSGGELDRWEKI) was defined as positive (22).…”