Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients.

The spontaneous immune responses against XAGE-1b (GAGED2a) were analyzed in non-small cell lung cancer (NSCLC) patients. An antibody response against XAGE-1b (GAGED2a) was observed in 10% (20/200) of NSCLC patients and in 19% (13/69) of stage IIIB/IV lung adenocarcinoma patients. A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b (GAGED2a) antibody-positive patients examined. Frequent antibody responses and CD4 and CD8 T-cell responses in XAGE-1b (GAGED2a) antibody-positive patients indicate the strong immunogenicity of the XAGE-1b (GAGED2a) antigen in NSCLC patients. We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b (GAGED2a) 18-31 peptide (14-mer) as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b (GAGED2a) 21-29 peptide (9-mer) as a CD8 T cell epitope. As for peptide recognition, CD4 and CD8 T-cell clones responded to naturally processed antigen. The CD4 T-cell clone recognized DCs pulsed with the synthetic protein or a lysate from XAGE-1b-transfected 293T cells. The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b (GAGED2a) and the appropriate HLA class I allele. These findings establish XAGE-1b (GAGED2a) as a promising target for a lung cancer vaccine.

Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination.

NY-ESO-1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY-ESO-1-expressing tumors with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and showed efficient induction of NY-ESO-1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE-A1, MAGE-A3, MAGE-A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme-linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription-polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY-ESO-1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6-tag and/or bacterial products included in a preparation of CHP-NY-ESO-1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine.

Branched-chain amino acid-enriched nutrients improve nutritional and metabolic abnormalities in the early post-transplant period after living donor liver transplantation.

BACKGROUND/PURPOSE: Malnutrition and metabolic disorder of patients undergoing living donor liver transplantation (LDLT) can affect post-transplant prognosis. The aim of this study was to establish whether perioperative usage of branched-chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of patients undergoing LDLT. METHODS: We designed a randomized pilot study (UMIN registration number; 000004323). Twenty-five consecutive adult elective LDLT recipients were enroled and divided into two groups: the BCAA group (BCAA-enriched nutrients, n = 12) and the control group (standard diet, n = 13). Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR), retinol binding protein (RBP), and prealbumin were regularly measured from 1 week before to 4 weeks after LDLT. Non-protein respiratory quotient (npRQ) was measured before and 4 weeks after LDLT. RESULTS: BTR and RBP improved considerably in the BCAA group compared with the controls. npRQ significantly increased from 1 week before LDLT to 4 weeks after LDLT in the BCAA group (0.77 ± 0.05 to 0.84 ± 0.06, P = 0.002), but not in the control group (0.78 ± 0.04 to 0.81 ± 0.05). CONCLUSIONS: Supplementation with BCAA-enriched nutrients might improve persistent nutritional and metabolic disorders associated with end-stage liver disease in the early post-transplant period, and consequently shorten the post-transplant catabolic phase after LDLT. A larger multicenter trial is needed to confirm these findings.