RESUMO
Dinutuximab is a monoclonal antibody administered to patients with high-risk neuroblastoma, usually after an autologous stem cell transplant. Dinutuximab is associated with immune mediated and neurologic toxicities, but fatal adverse events are rare. A case is presented of high-risk neuroblastoma with development of encephalopathy shortly after the first course of dinutuximab. The patient had extensive evaluation for etiology of the symptoms and received aggressive interventions, but ultimately expired. Postmortem diagnosis of anti-N-methyl D-aspartate receptor encephalitis, an autoimmune phenomenon often triggered by infection or malignancy, was made. The potential association of autoimmune encephalitis with dinutuximab and with previous autologous transplant is discussed.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Neuroblastoma/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/induzido quimicamente , Humanos , Lactente , Masculino , Neuroblastoma/patologia , PrognósticoRESUMO
Since the first anecdotal reports of dramatic tumor responses following a viral infection in early 1900s, the field of oncolytic virotherapy has evolved at a rapid pace finally making its way into clinical trials. A large number of both wild-type and genetically altered viruses with a preferential replication-competency for tumor cells have been studied in tissue cultures, animal models and in humans, with an ever increasing repertoire of new viruses being added to this pool. Although oncolytic viruses have caused dramatic antitumor responses in cell cultures and mouse models, their clinical effects in humans have been modest. Therefore, the current research is focused on understanding the mechanisms by which viruses kill tumor cells, the barriers to successful viral delivery and penetration into tumor cells, the role of the immune system in viral oncolysis and generating stronger target specific and replication competent viruses. Osteosarcoma is a challenging malignancy to identify novel targets for therapy due to its complex genetic make-up. Oncolytic virotherapy may be a promising approach as a novel therapeutic, not dependent on consistent expression of a single target. In this review we summarize the supportive evidence and rationale for use of viral oncolysis in osteosarcoma along with the specific challenges it may face.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/terapia , Neoplasias Pulmonares/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Osteossarcoma/terapia , Animais , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/patologia , Terapia Combinada , Vetores Genéticos/uso terapêutico , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Vírus Oncolíticos/patogenicidade , Osteossarcoma/imunologia , Osteossarcoma/patologia , Replicação ViralRESUMO
This case underscores the difficulty in diagnosis of bone marrow failure disorders, as the presentation of disease can be inconsistent, complicated by complex and ever-expanding genetic etiologies. A patient who presents with bone marrow failure and pancreatic insufficiency raises the question of Shwachman-Diamond syndrome (SDS) or a new condition which resembles SDS.
RESUMO
Survival outcomes for osteosarcoma have plateaued since the 1980s, and patients with relapsed or refractory disease have a particularly dismal outcome. Treatment options for these patients are limited primarily due to the paucity of effective therapeutics. Immune therapies such as tumor vaccines and traditional antigen-targeted monoclonal antibodies have had limited success in solid tumors. The recent discovery of novel immune checkpoint blockade strategies and their success in adult cancers has revitalized the use of immunotherapy strategies for the treatment of solid tumors. This paper summarizes existing data supporting the use of immune therapies in osteosarcoma and the progress of this class of drugs in osteosarcoma therapy.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Ósseas/terapia , Vacinas Anticâncer/imunologia , Imunoterapia/métodos , Osteossarcoma/terapia , Adulto , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/mortalidade , Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Osteossarcoma/imunologia , Osteossarcoma/mortalidade , Análise de SobrevidaRESUMO
The diverse roles of chemokines in normal immune function and many human diseases have motivated numerous investigations into the structure and function of this family of proteins. Recombinant chemokines are often used to study how chemokines coordinate the trafficking of immune cells in various biological contexts. A reliable source of biologically active protein is vital for any in vitro or in vivo functional analysis. In this chapter, we describe a general method for the production of recombinant chemokines and robust techniques for efficient refolding that ensure consistently high biological activity. Considerations for initiating development of protocols consistent with Current Good Manufacturing Practices (cGMPs) to produce biologically active chemokines suitable for use in clinical trials are also discussed.
Assuntos
Engenharia de Proteínas/métodos , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Quimiotaxia , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão/métodos , GMP Cíclico/metabolismo , Dissulfetos/química , Escherichia coli/genética , Ressonância Magnética Nuclear Biomolecular , Processamento de Proteína Pós-Traducional , Redobramento de Proteína , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Reprodutibilidade dos TestesRESUMO
Desmoplastic small round cell tumor (DSRCT) is a rare but highly fatal malignancy. Due to the rarity of this neoplasm, no large population based studies exist. Procedure. This is a retrospective cohort analysis. Incidence rates were calculated based on sex and ethnicity and compared statistically. Gender-, ethnicity-, and treatment- based survival were calculated using the Kaplan-Meier method. Results. A total of 192 cases of DSRCT were identified. Peak incidence age was between 20 and 24 years. Age-adjusted incidence rate for blacks was 0.5 cases/million and for whites was 0.2 cases/million (P = 0.037). There was no statistically significant difference in survival based on gender or ethnicity. When adjusted for age, there was no statistically significant difference in survival amongst patients who received radiation therapy compared to those who did not (HRadj = 0.73; 95% CI 0.49, 1.11). There was a statistically significant survival advantage for patients who received radiation after surgery compared to those who did not (HR 0.49; 95% CI 0.30, 0.79). Conclusion. DSRCT is more common in males and in people of African-American descent. Although overall survival remains poor, radiation therapy following surgery seems to improve outcome in these patients.
RESUMO
Oncolytic virotherapy has shown exciting promise for the treatment of many types of solid tumors. Pediatric sarcomas are an aggressive type of pediatric malignancy known to show limited responsiveness to current therapies, leading to unacceptably high morbidity and mortality. Oncolytic viruses have only recently been used for the treatment of this challenging cancer, and results have been encouraging. Five clinical trials are currently open evaluating the use of oncolytic viruses in pediatric malignancies. Advances in genetic engineering of the viruses include improving the ability of the virus to infect tumor cells, engineering the virus with transgenes which improve the virus' ability to kill tumor cells and manipulating the virus to enhance concomitantly administered therapies. Further understanding of the antiviral immune response and a viral induced anti-tumor immune response will permit a maximization of oncolytic virotherapy.