PubMed · 4125651
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R A Thompson, R H White. 1973-09-22. Partial lipodystrophy and hypocomplementaemic nephritis.. https://doi.org/10.1016/s0140-6736(73)92516-6
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The SSX2 gene encodes the tumor-specific antigen HOM-MEL-40/SSX2 expressed in a broad spectrum of tumors of different origin, against which humoral and CD8+ T-cell-mediated MHC-I-restricted responses have been demonstrated. Searching for promiscuous MHC-II-restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified a HOM-MEL-40/SSX2-derived pentadecamer epitope (p45-59) that induced specific CD4+ T-cell responses restricted by the HLA-DRB1 subtypes *0701, *1101 and *1302 that have a cumulative prevalence of approximately 25% in the Caucasian population. The CD4+-mediated response against p45-59 and its DR restriction was demonstrated by inhibition with anti-CD4 and HLA-DR antibodies, respectively, and by blocking experiments using HLA-specific antibodies. The natural processing and presentation of p45-59 was demonstrated by recognition of the SSX2+ melanoma cell line Me 275 as well as autologous and allogeneic dendritic cells pulsed with whole-protein SSX2 by T cells with specificity for p45-59. p45-59 was able to induce responses in 3/6 breast cancer patients and 1/5 healthy controls. No correlation was found between CD4+ T-cell responses against p45-59 reactivity and anti-SSX2 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. p45-59 holds promise as a broadly applicable peptide vaccine for patients with SSX2-positive neoplasms.
Gastric cancer has the highest mortality rate and the second-highest morbidity rate of all malignant tumors in China. Since cancer/testis (CT) antigens are expressed in various types of human tumors but generally not in normal tissue except for testis, they are promising antigens for cancer immunotherapy. NY-ESO-1, in particular, is the most immunogenic of the CT antigens. To study the feasibility of developing a CT antigen vaccine for gastric cancer, 101 gastric cancer samples were analyzed for the presence of NY-ESO-1 mRNA and that of 10 other CT antigen genes. Twelve out of 101 samples (11.9%) were found to be NY-ESO-1 mRNA-positive, 11 of them from advanced stage patients. In 7 of the 12 NY-ESO-1 mRNA-positive samples, the NY-ESO-1 protein was also detected by immunohistochemistry. An autologous humoral immune response to NY-ESO-1 was detected in 6 of 12 advanced stage NY-ESO-1 mRNA-positive patients, indicating that NY-ESO-1 is immunogenic in advanced stage gastric cancer. The serum from a patient with an NY-ESO-1 negative but LAGE-1 positive tumor was also found to be NY-ESO-1 antibody positive, possibly due to cross-reactivity between NY-ESO-1 and LAGE-1. All NY-ESO-1 mRNA-positive gastric cancer samples also expressed one to seven additional CT genes, revealing a tendency toward a clustered expression pattern, regardless of disease stage. About 74% of the samples expressed at least one CT antigen, most frequently MAGE-3 (41.6%). NY-ESO-1 and MAGE-3 are thus potential targets for a multivalent CT antigen vaccine.
The objective of this study was to further explore previously identified effects of supplemental ribonucleotides on infant immune status as measured by antibody responses to routine infant immunizations. Infants were randomized to a milk-based formula with (FN, n = 138) or without (F, n = 147) 72 mg ribonucleotides/L. A cohort of human milk-fed (HMF, n = 192) infants was also followed. Subjects were given Haemophilus influenzae type b (Hib), diphtheria tetanus acellular pertussis, and oral poliovirus vaccinations at 2, 4, and 6 mo of age, and specific antibody responses were assessed at 2, 6, 7, and 12 mo. Growth and safety data were also monitored. Using a two-group repeated measures analysis (RMA), FN-fed infants had significantly higher poliovirus type 1 neutralizing antibody (PV-VN1) responses than F-fed infants (p = 0.045). Using three-group RMA, PV-VN1 responses in HMF infants were not different from FN-fed infants, while HMF-fed infant PV-VN1 responses were significantly higher than F-fed infants at 6 (p = 0.0004) and 12 mo (p = 0.0001). FN-fed infants had responses to Hib Farr, diphtheria, tetanus toxoid, oral poliovirus-specific IgA, and PV-VN3 not significantly different from those of F and HMF infants. Growth, gastrointestinal tolerance, and adverse events were equivalent among the three groups. The FN-associated increase in PV-VN1 response and nonstatistically significant trends toward increased Hib and diphtheria antibody responses were consistent with observations from earlier studies, indicating immune benefits of nucleotide supplementation of infant formula.