RESUMO
With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.
Assuntos
Neoplasias/epidemiologia , História do Século XXI , Humanos , Emirados Árabes UnidosRESUMO
PURPOSE: Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine. EXPERIMENTAL DESIGN: Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer overexpressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles. RESULTS: Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively. CONCLUSION: We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
Assuntos
Células Dendríticas/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/terapia , Proteína Supressora de Tumor p53/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Adulto , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Estudos de Coortes , Terapia Combinada , Células Dendríticas/transplante , Fadiga/etiologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Antígeno HLA-A2/imunologia , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Interleucina-2/imunologia , Estimativa de Kaplan-Meier , Linfopenia/etiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Fatores de Risco , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/efeitos adversosRESUMO
BACKGROUND: Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the von Hippel-Lindau (VHL) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides. METHODS: Six patients with advanced RCC and mutated VHL genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock. RESULTS: Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively. CONCLUSIONS: The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. TRIAL REGISTRATION: 98C0139.