Human monoclonal IgM antibodies with apoptotic activity isolated from cancer patients

Brändlein, Stephanie; Lorenz, Judith; Ruoff, Nele; Hensel, Frank; Beyer, Ines; Muller, J.Y.; Neukam, K.; Illert, B.; Eck, Matthias; Müller‐Hermelink, Hans Konrad; Vollmers, H. Peter

doi:10.3233/hab-2002-11401

Cited by 28 publications

(31 citation statements)

References 42 publications

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“…This deadly process is characterized by an extreme intracellular accumulation of lipid vesicles. This lipoptotic effect is specific for the antibody SAM-6, because other apoptotic human IgMs (10,11) or the murine antibody CD95/Fas do not show this unique feature.…”

Section: Discussionmentioning

confidence: 99%

“…Carcinoma cell lines 23132/87 and BXPC-3 were cultured as described previously (11), and nasal septum squamous cell carcinoma cell line RPMI-2650 (DSMZ ACC287, Braunschweig, Germany) was cultured in RPMI-1640 (PAA, Vienna, Austria) supplemented with 10% FCS, 2 mM glutamine, and penicillin/streptomycin (both 1%). Normal human nasal epithelial cells HNEpC-c (PromoCell GmbH, Heidelberg, Germany) were cultured in a special airway epithelial cell growth medium with SupplementMix (PromoCell).…”

Section: Methodsmentioning

confidence: 99%

“…The Cell Death Detection ELISA PLUS (Roche, Mannheim, Germany) was performed as described previously (11).…”

Section: Methodsmentioning

confidence: 99%

“…All tumor-specific antibodies were found to have some features in common. Regardless of tumor type or lymphocyte source, they were of IgM isotype, germ-line coded, and produced by CD5ϩ lymphocytes (10,11). Furthermore, they bound to carbohydrate structures on posttranscriptionally modified cell-surface receptors (10,(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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Lipoptosis

et al. 2004

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A balanced lipid metabolism is crucial for all cells. Disturbance of this homeostasis by nonphysiological intracellular accumulation of fatty acids can result in apoptosis. This was proven in animal studies and was correlated to some human diseases, like lipotoxic cardiomyopathy. Some metabolic mechanisms of lipo-apoptosis were described, and some causes were discussed, but reagents, which directly induce lipo-apoptosis, have thus far not been identified. The human monoclonal IgM antibody SAM-6 was isolated from a stomach cancer patient by using the conventional human hybridoma technology (trioma technique). The addition of SAM-6 to tumor cells leads to an increase in the intracellular accumulation of neutral lipids, followed by tumor cell apoptosis. The antibody SAM-6 does not react with noncancerous human epithelial and fibroblastic cells, because the M r 140,000 membrane molecule, recognized by the antibody, is specifically expressed on human malignant cells. The antibody is coded by the germ-line genes IgHV3-30.3*01 and IgLV3-1*01 and is a component of the innate immunity to cancer. In this article, we describe an antibodyinduced tumor-specific cell death, named lipoptosis. This is, to our knowledge, the first description of this specific form of lipo-apoptosis as an antibody-mediated mechanism of tumor cell killing.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The Cell Death Detection ELISA PLUS (Roche, Mannheim, Germany) was performed as described previously (11).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipoptosis

et al. 2004

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“…In a previous study, five human monoclonal IgM antibodies from cancer patients were established (23). Antibody LM-1 was isolated from a patient with lung cancer, antibodies PM-1 and PM-2 were isolated from a patient with pancreatic cancer, and antibodies CM-1 and CM-2 were isolated from a patient with colon carcinoma.…”

Section: Protective Humoral Responses In Cancermentioning

confidence: 99%

Protective autoimmunity in cancer (Review)

Toubi

Shoenfeld²

2007

Oncol Rep

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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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Human monoclonal IgM antibodies with apoptotic activity isolated from cancer patients

Cited by 28 publications

References 42 publications

Lipoptosis

Lipoptosis

Protective autoimmunity in cancer (Review)

Naturally Occurring Antibodies Directed Against Carbohydrate Tumor Antigens

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