RESUMEN
N-Acetyl-D-glucosamine-substituted glycoconjugates (GCJs) with the polyamidoamine (GN8P) or calix[4]arene (GN4C) scaffold represent ligands for NKR-P1 molecule and induce NK cell-mediated cytotoxicity in vitro. The in vivo effect of these GCJs on mouse melanoma model was determined when administered either alone or in combination with non-specific immunostimulator keyhole limpet hemocyanin (KLH). All types of treatment significantly reduced the tumor growth on day 23, while GN4C as well as KLH were effective continuously (from day 14). The GN4C also induced the longest mean survival time (46.3 ± 11.1 d), followed by KLH+GN4C (36.4 ± 12.1), KLH (35.6 ± 6.5), KLH+GN8P (35.6 ± 6.7), and GN8P (32.4 ± 7.0), compared to controls (29.8 ± 3.6). The B16F10 specific cytotoxicity of peripheral blood cells was significantly elevated by both KLH and GN8P, whereas not by GN4C. KLH increased the effect of the GN4C, but did not influence that of GN8P. GN4C was proved to exert anticancer activity in mouse melanoma model. The combination of KLH with GCJs did not generate synergism.
Asunto(s)
Acetilglucosamina/química , Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos/uso terapéutico , Glicoconjugados/uso terapéutico , Hemocianinas/uso terapéutico , Melanoma/tratamiento farmacológico , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Glicoconjugados/química , Humanos , Masculino , Melanoma/patología , Ratones , Ratones Endogámicos C57BL , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: At present, no reliable in vitro test is available to monitor the success of specific venom immunotherapy (VIT) in preventing insect venom anaphylaxis. We investigated usefulness of the basophil activation test (BAT) in predicting the outcome of sting challenge in bee venom-allergic patients after VIT. PATIENTS AND METHODS: Twenty-one patients with bee venom anaphylaxis at the end of VIT and 6 control participants were enrolled. BAT (flow-cytometric evaluation of allergen-induced expression of CD63), skin testing, and specific immunoglobulin (Ig) E determination were performed prior to sting challenge. RESULTS: Five of the 21 patients (23.8%) reacted to sting challenge. At a bee venom concentration of 100 ng/mL, the mean proportion of basophils expressing CD63 was 56% in reactors and 13.2% in nonreactors (P = .0321). Four of the 5 reactors had positive results and 14 of the 16 nonreactors had negative results. Thus, using 18.4% and 21.6% (receiver operating characteristic curve analysis) as the cutoff for expression of the CD63 marker, the positive and the negative predictive values were 67% and 93%, respectively, and specificity and sensitivity for BAT were 80% and 83%, respectively. However, at a concentration of 1000 ng/mL, no significant differences in basophil activation were observed between reactors and nonreactors. CONCLUSION: We found BAT to be a helpful tool in predicting the clinical sensitivity of bee venom-allergic patients after VIT (correlation between BAT at submaximal venom concentration and sting challenge).