RESUMO
NY-ESO-1 is a cancer-testis antigen and an attractive target for immunotherapy in patients with different malignancies. Here we report the results of a phase I clinical study of intensive course NY-ESO-1 peptide vaccination, evaluating the safety, immunogenicity and clinical response in HLA-A2 positive patients with NY-ESO-1 expressing cancers. Of 20 patients enrolled in the trial, 14 completed at least 2 cycles of immunization and were evaluable for clinical and immunological response. Five of these evaluable patients were treated in cohort 1 (baseline seropositive) and 9 patients were treated in cohort 2 (baseline seronegative). During vaccination, NY-ESO-1-specific CD8+ T-cells were induced in 3 of 9 baseline seronegative patients. In patients with pre-existing antigen-specific CD8+ T-cells, their number increased or remained stable. In contrast to previous immunization protocols with less intensive immunization schedules, we observed a rapid induction of high magnitude NY-ESO-1 peptide-specific T-cell responses detectable already on day 15-22 of immunization. A specific immune response of high magnitude and early onset may be more effective in eliminating minimal residual disease in adjuvant treatment situations and in preventing tumor progression due to immune escape mechanisms.
Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/administração & dosagem , Antígeno HLA-A2/metabolismo , Imunoterapia , Proteínas de Membrana/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias/terapia , Fragmentos de Peptídeos/imunologia , Adolescente , Adulto , Idoso , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Estudos de Coortes , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Humanos , Hipersensibilidade Tardia/imunologia , Imunização , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Resultado do TratamentoRESUMO
A melanoma patient with brain metastases was treated by gamma-knife radiosurgery and immunotherapy with autologous tumor-lysate-loaded dendritic cells (DC). Ten years after the combined treatment, the patient remains in complete remission. Remarkable immunologic correlates to the clinical development were the transient induction of NY-ESO-1 antibody and the durable expansion of MAGE-A1p161-169 EADPTGHSY-specific CD8+ T cells. Although the induction of NY-ESO-1 antibody most likely resulted from gamma-knife-mediated "auto-vaccination," the persistence of circulating MAGE-A1-specific T cells, which are still detectable ex vivo in the absence of any tumor manifestation, coincides with DC-based vaccination administered monthly until today.