Initial characterization of the apoptosis-inducing receptor for natural human anti-neuroblastoma IgM

David, Kerstin A.; Heiligtag, Sven; Ollert, Markus; Teppke, Manfred; Vogel, Carl‐Wilhelm; Bredehorst, Reinhard

doi:10.1002/1096-911x(20010101)36:1<251::aid-mpo1062>3.0.co;2-z

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…31 The target antigen has an apparent molecular mass of 260 kDa and is a surface protein containing polypeptide sequences related to the c subunit of the human mitochondrial ATP synthase and to heat shock protein 90. 32 These IgM antibodies may represent a novel therapeutic tool for neuroblastoma treatment.…”

Section: Tumor Cell Recognition By Antibodiesmentioning

confidence: 99%

“…Binding of natural IgM antibodies to neuroblastoma cells induces apoptosis; furthermore, in vivo studies have shown that these antibodies exert potent antitumor activity 31. The target antigen has an apparent molecular mass of 260 kDa and is a surface protein containing polypeptide sequences related to the c subunit of the human mitochondrial ATP synthase and to heat shock protein 90 32. These IgM antibodies may represent a novel therapeutic tool for neuroblastoma treatment.…”

Section: Tumor Cell Recognition By Antibodiesmentioning

confidence: 99%

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Immunogenicity of Human Neuroblastoma

Prigione

Corrias

Airoldi

et al. 2004

Annals of the New York Academy of Sciences

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Neuroblastoma (NB) is a neuroectodermal tumor that affects children in the first years of life. Half of NB cases present with metastatic disease at diagnosis and have a poor prognosis, in spite of the most advanced chemotherapeutic protocols combined with autologous hematopoietic stem cell transplantation. Among the new avenues for NB treatment that are being explored, immunotherapy has attracted much interest. Emphasis has been placed on monoclonal antibodies directed to tumor-associated antigens--in particular the disialoganglioside GD2--that have been tested in the clinical setting with promising results. In addition, stimulation of cell-mediated antitumor effector mechanisms have been attempted-for example, by recombinant interleukin (IL)-2 administration. Nonetheless, the issue of the immunogenicity of human NB cells has never been thoroughly addressed. Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules. As such, NB cells are likely to be ignored by the host T cell compartment, since expression of HLA and costimulatory molecules on antigen presenting cells are sine qua non conditions for efficient peptide presentation to T cells and for the subsequent activation and clonal expansion of the latter cells. Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-gamma. Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism. Collectively, these results indicate that the immunogenicity of human NB cells is very low but suggest that manipulation by cytokine administration or gene transfer can increase their immunogenic potential. On the other hand, NB cells represent an excellent target for natural killer cells, the potential role of which in immunotherapy of NB is now being investigated.

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Section: Tumor Cell Recognition By Antibodiesmentioning

confidence: 99%

Section: Tumor Cell Recognition By Antibodiesmentioning

confidence: 99%

Immunogenicity of Human Neuroblastoma

Prigione

Corrias

Airoldi

et al. 2004

Annals of the New York Academy of Sciences

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“…Landmark studies from Rosenberg's group demonstrated that incubation of normal circulating lymphocytes with recombinant (r)IL-2 triggered expansion of the so called "lymphokine activated killer" (LAK) cells, showing HLA-unrestricted cytotoxicity against virtually all tumor targets [78]. Subsequent clinical studies performed in cancer patients using autologous LAK cells associated with rIL-2 proved the therapeutic efficacy of this approach in melanoma and renal cell carcinoma patients, but also its severe toxicity [78].…”

Section: Cytokine Therapy Of Human Neuroblastomamentioning

confidence: 99%

Molecularly Guided Therapy of Neuroblastoma: A Review of Different Approaches

Tonini¹,

Pistoia²

2006

CPD

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Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric tumors and affects more than ten thousand children a year. It originates from the sympathetic nervous system and is characterized by heterogeneous pathological and clinical presentation. Stage 4 NB represents approximately 50% of the cases and shows metastatic dissemination at onset; its prognosis is grim, with 20% of the patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy with autologous hematopoietic stem cell support. Novel therapeutic strategies are urgently needed to improve the prognosis of stage 4 NB patients. Here we review the most promising approaches to NB treatment that have already reached clinical testing or have proved to be successful in preclinical models of the disease. All of these approaches are molecularly guided, since their rational development has benefited from the enormous amount of information on the biology of neuroblastoma gathered through molecular biology and genetics studies. The following topics are reviewed: MYCN oncogene amplification as parameter for therapeutic decision, minimal residual disease, immunotherapy, gene therapy, differentiation and apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for generating novel therapeutic approaches. Although several efforts are still needed to reach a significant cure of patients with neuroblastoma, molecularly guided approaches have opened new ways to neuroblastoma treatment and can represent useful models for other cancers of either childhood or adulthood.

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