Treatment of neuroblastoma with human natural antibodies

Erttmann, R.

doi:10.1016/j.autrev.2008.03.014

Cited by 13 publications

(13 citation statements)

References 20 publications

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“…Several treatments with plasma containing high titers of anti-neuroblastoma cytotoxic antibodies led to a considerable life prolongation in one patient and curation from the tumor in another patient. 61 Large-scale screening of sera from healthy donors revealed that a considerably small percentage of approximately 1-2% donors in the Western world have high titers of cytotoxic antibodies against several human tumors like neuroblastoma and melanoma (Schwartz-Albiez, unpublished results). Although only few donors carry cytotoxic anti-tumor antibodies of IgM isotype in their peripheral blood, almost all healthy persons have anti-tumor binding antibodies.…”

Section: Tumor-associated Carbohydrate Antigens As Target Structures mentioning

confidence: 95%

“…58,59 A successful treatment of neuroblastoma with these antibodies of healthy donors was performed in a nude rat model bearing solid human neuroblastoma tumors 57,60 and further in a small clinical study of nine neuroblastoma children patients suffering from late stage neuroblastoma. 61 Neuroblastoma patients had undergone several different treatments like chemotherapy, surgery, bone marrow transplantations and application of anti-GD2 monoclonal antibodies before they were included in this study. Several treatments with plasma containing high titers of anti-neuroblastoma cytotoxic antibodies led to a considerable life prolongation in one patient and curation from the tumor in another patient.…”

Section: Tumor-associated Carbohydrate Antigens As Target Structures mentioning

confidence: 99%

“…This strategy, using pooled anti-neuroblastoma cytotoxic plasma, had been prescribed for the treatment of children patients suffering from neuroblastoma. 61 Isolation of anti-carbohydrate tumor-directed IgM antibodies from pooled immunoglobulin fractions requires a sophisticated separation procedure, in particular when these preparations shall be produced at industrial large scale for tumor treatment in a standardized form.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

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Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Schwartz‐Albiez

2012

Advances in Experimental Medicine and Biology

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Healthy persons carry within their pool of circulating antibodies immunoglobulins preferentially of IgM isotype, which are directed against a variety of tumor-associated antigens. In closer scrutiny of their nature, some of these antibodies could be defined as naturally occurring antibodies due to the germline configuration of the variable immunoglobulin region. The majority of these immunoglobulins recognize carbohydrate antigens which can be classified as oncofetal antigens. Many of these IgM antibodies present in the peripheral blood circulation can bind to tumor cells and of these a minor portion are also able to destroy tumor cells by several mechanisms, as for instance complement-mediated cytolysis or apoptosis. It was postulated that anti-carbohydrate antibodies are part of an anti-tumor immune response, while their presence in the peripheral blood of healthy donors is still waiting for a plausible explanation. It may be that recognition of defined epitopes, including carbohydrate sequences, by naturally occurring antibodies constitutes the humoral arm of an anti-tumor immune response as part of the often postulated tumor surveillance. The cytotoxic capacity of these antibodies inspired several research groups and pharmaceutical companies to design novel strategies of immunoglobulin-based anti-tumor immunotherapy.

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Section: Tumor-associated Carbohydrate Antigens As Target Structures mentioning

confidence: 95%

Section: Tumor-associated Carbohydrate Antigens As Target Structures mentioning

confidence: 99%

Section: Therapeutic Approachesmentioning

confidence: 99%

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Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Schwartz‐Albiez

2012

Advances in Experimental Medicine and Biology

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“…Furthermore, human immunotherapy has, so far, primarily focused on the use of IgG antibodies that target specific tumour‐associated antigens and has largely overlooked the potential importance of IgM isotypes . The latter has been shown to provide extended tumour immunosurveillance as well as anti‐tumour cytotoxic activity in other organisms, and IgM antibody therapy has been shown to reduce neuroblastoma and melanoma in humans . IgM antibodies detect cancer precursor stages (i.e.…”

Section: Transmissible Cancer Invokes Adaptive Changes and Responses mentioning

confidence: 99%

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

et al. 2018

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Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease (DFTD), a transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii), provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts. Here we provide an overview of parasite-induced host life history (LH) adaptations, then both phenotypic plasticity of LH responses and changes in allele frequencies that affect LH traits of Tasmanian devils in response to DFTD are discussed. We conclude that akin to parasites, cancer can directly and indirectly affect devil LH traits and trigger host evolutionary responses. Consequently, it is important to consider oncogenic processes as a selective force in wildlife.

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“…IgM of healthy donors can convey cytotoxic activity against neuroblastoma . This finding had prompted a small clinical study in which nine relapsed, high‐risk neuroblastoma children patients were treated with plasma of healthy persons with high in vitro cytotoxicity against a neuroblastoma cell line.…”

mentioning

confidence: 97%

Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors

Devarapu

Mamidi

Plöger

et al. 2016

Intl Journal of Cancer

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A small percentage of healthy donors identified in the Western population carry antibodies in their peripheral blood which convey cytotoxic activity against certain human melanoma and neuroblastoma cell lines. We measured the cytotoxic activity of sera and plasmas from healthy donors on the human neuroblastoma cell line Kelly and various melanoma cell lines. Antibodies of IgM isotype, presumably belonging to the class of naturally occurring antibodies, exerted cytotoxic activity in a complement-dependent fashion. Apart from complement-dependent tumor cell lysis, we observed C3 opsonization in all tumor cell lines upon treatment with cytotoxic plasmas. Cell lines tested primarily expressed membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59 to various extents. Blocking of mCRPs by monoclonal antibodies enhanced cell lysis and opsonization, though some melanoma cells remained resistant to complement attack. Epitopes recognized by cytotoxic antibodies were represented by gangliosides such as GD2 and GD3, as evidenced by cellular sialidase pretreatment and enhanced expression of distinct gangliosides. It remains to be clarified why only a small fraction of healthy persons carry these antitumor cytotoxic antibodies. oligosaccharide-specific monoclonal antibodies or by vaccination with tumor-associated oligosaccharides. For example, treatment with antiganglioside antibodies caused regression of neuroblastoma, 3,4 and clinical trials have been performed using the anti-GD3 monoclonal antibody (mAb) R24 for passive immunization in melanoma patients. 5 In melanoma patients, the level of antiganglioside antibodies was significantly increased after vaccination with a cocktail of gangliosides, and antibody titers correlated with patients' survival. 6 Within the Western population a small proportion of healthy persons carry, within their pool of circulating immunoglobulins, antibodies, preferentially of IgM isotype which can cause a complement-mediated cytolysis of human neuroblastoma cells. 7,8 There are strong indications that these antibodies belong to the class of naturally occurring antibodies (nAb) that are present without external stimulation as products of germ-line encoded genes of the variable region 9,10 and further that a majority of IgM nAb react with carbohydrate antigens. IgM nAb are involved in homeostasis by clearance of damaged or modified intracellular plasma proteins, oxidized lipoproteins or dying cells. 11 Functions attributed to IgM are neutralization, opsonization and complement activation. IgM nAb bind to invading pathogens, which results in complement activation and lysis of the invaders as first line of defense. 11

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Treatment of neuroblastoma with human natural antibodies

Cited by 13 publications

References 20 publications

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors

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