RESUMO
BACKGROUND: Immunotherapy using autologous dendritic cell (DC) vaccination has not been systematically evaluated in osteosarcoma. We therefore conducted a phase I trial to assess feasibility, safety and tumour-specific immune responses in patients with relapsed disease. PATIENTS AND METHODS: Of 13 recruited patients with relapsed osteosarcoma, 12 received 3 weekly vaccines of autologous DCs matured with autologous tumour lysate and keyhole limpet haemocyanin (KLH), to a maximum of 6 vaccinations. An additional 3 paediatric patients afflicted with other tumour types and with relapsed disease received vaccines generated with identical methodology. Immune responses were assessed using an ELISpot assay for the detection of interferon gamma, whilst interleukin-2 and granzyme B were additionally assessed in cases where interferon-γ responses were induced. RESULTS: In total 61 vaccines, of homogeneous maturation phenotype and viability, were administered with no significant toxicity. Only in 2 out of 12 treated osteosarcoma cases was there an induction of specific T-cell immune response to the tumour, whilst a strong but non-specific immune response was induced in 1 further osteosarcoma patient. Immune response against KLH was induced in only 3 out of 12 osteosarcoma patients. In contrast, three additional non-osteosarcoma patients showed significant T-cell responses to vaccine. CONCLUSION: We have shown the strategy of DC vaccination in relapsed osteosarcoma is safe and feasible. However, significant anti-tumour responses were induced in only 2 out of 12 vaccinated patients with no evidence of clinical benefit. Comparison of results with identically treated control patients suggests that osteosarcoma patients might be relatively insensitive to DC-based vaccine treatments.
Assuntos
Vacinas Anticâncer , Osteossarcoma/imunologia , Osteossarcoma/terapia , Linfócitos T/citologia , Adolescente , Adulto , Células Dendríticas/citologia , Estudos de Viabilidade , Feminino , Granzimas/biossíntese , Hemocianinas/química , Humanos , Imunoterapia/métodos , Interferon gama/biossíntese , Interleucina-2/biossíntese , Masculino , Osteossarcoma/metabolismo , Fenótipo , Recidiva , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the frequency of retinal lesions in patients with chronic granulomatous disease (CGD) and to seek such lesions in carriers. STUDY DESIGN: Seventy-four individuals from 33 families were recruited; 38 had CGD (30 X-linked and 8 autosomal recessive inheritance). All participants (including 33 control subjects) underwent measurement of visual acuity, anterior segment examination by slit lamp, and dilated funduscopy. RESULTS: Nine of 38 (23.7%) of the affected children had chorioretinal lesions compared with 0 of 33 control subjects. All 9 were known to have X-linked CGD and absent gp91(phox). The "typical" retinal abnormality consisted of "punched out" chorioretinal lesions associated with pigment clumping lying along major retinal vessels. Unexpectedly, 3 XL-CGD asymptomatic carriers also had typical chorioretinal lesions. CONCLUSION: Retinal lesions are relatively common in patients with XL-CGD and may interfere with vision and thus should be sought in such patients.