Characterization of the Colorectal Antigen IOR-C2

Vázquez, Ana María; Tormo, B; Velandia, Alvaro; Giscombe, Ricardo; Ansotegui, Ignacio J.; Jeddi-Tehrani, Mahmood; Pérez, Rolando; Mellstedt, Håkan; Biberfeld, Peter

doi:10.1089/hyb.1992.11.245

Cited by 17 publications

(26 citation statements)

References 20 publications

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“…11), 14F7 anti-idiotypic 4G9 mAb (murine IgG1, n; ref. 18), iorC5 mAb (murine IgG1, n) that recognizes a glycoprotein expressed in colorectal cancer cells (19) and chimeric P3 (human IgG1, n), an anti-NGc-containing gangliosides and sulfatides mAb (20), were purified by Protein A Affinity Chromatography (Pharmacia) and analyzed by SDS-PAGE under reducing conditions. F(ab ¶) 2 and Fab fragments antibodies were obtained using a standard procedure described previously (21).…”

Section: Methodsmentioning

confidence: 99%

Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity

Roque-Navarro

Chakrabandhu

León

et al. 2008

Molecular Cancer Therapeutics

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Gangliosides have been involved in multiple cellular processes such as growth, differentiation and adhesion, and more recently as regulators of cell death signaling pathways. Some of these molecules can be considered as tumor-associated antigens, in particular, N-glycolyl sialic acid -containing gangliosides, which are promising candidates for cancer-targeted therapy because of their low expression in normal human tissues. In this study, we provided the molecular and cellular characterization of a novel cell death mechanism induced by the anti-NGcGM3 14F7 monoclonal antibody (mAb) in L1210 murine tumor cell line but not in mouse normal cells (B and CD4 + T lymphocytes) that expressed the antigen. Impairment of ganglioside synthesis in tumor cells abrogated the 14F7 mAb cytotoxic effect; however, exogenous reincorporation of the ganglioside did not restore tumor cell sensitivity to 14F7 mAb-induced cytotoxicity. 14F7 F(ab ¶) 2 but not Fab fragments retained the cytotoxic capacity of the whole mAb. By contrary, other mAb, which recognizes N-glycolylated gangliosides, did not show any cytotoxic effect. These mAbs showed quite different capacities to bind NGcGM3-positive cell lines measured by binding inhibition experiments. Interestingly, this complementindependent cell death mechanism did not resemble apoptosis, because no DNA fragmentation, caspase activation, or Fas mediation were observed. However, NGcGM3 ganglioside-mediated 14F7 mAb-induced cell death was accompanied by cellular swelling, membrane lesion formation, and cytoskeleton activation, suggesting an oncosislike phenomenon. This novel mechanism of cell death lets us to support further therapeutic approaches using NGcGM3 as a molecular target for antibody-based cancer immunotherapy.

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Section: Methodsmentioning

confidence: 99%

Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity

Roque-Navarro

Chakrabandhu

León

et al. 2008

Molecular Cancer Therapeutics

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“…As isotype-matched controls, ior cea-1 (anti-carcinoembrionic antigen) and ior C5 (against a glycoprotein expressed on human colorectal cells) MAbs and their F(ab') 2 fragments were used. 19,20 Alkaline phosphatase-conjugated antibodies against human IgM or IgG were used as secondary antibodies. Absorbance was measured at 405 nm in an ELISA reader (Organon Teknika, Salsburg, Austria).…”

Section: Study Design and Patient Evaluationmentioning

confidence: 99%

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

Neninger¹,

Díaz²,

Torre³

et al. 2007

Cancer Biology & Therapy

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ABSTRACT1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1 MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some human tumors. Preparations containing this Ab2 were capable to induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a Phase I clinical trial to evaluate the toxicity and humoral immune response elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible patients were those who after received chemotherapy and/or radiotherapy had partial or complete response to treatment. Patients received four biweekly injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six doses at 28-day intervals, and later the patients who maintained a good performance status were reimmunized. Six patients with limited-stage disease and three with extensive-stage disease were enrolled in the study. Most of the patients who received at least four doses of 1E10 vaccine developed strong specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside. Antibodies able to react with lung carcinoma tissue sections were detected in sera from vaccinated patients. A prolonged survival was observed in several patients treated with the anti-idiotype vaccine. No evidence of serious adverse effects was found.

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“…Titer was defined as the highest serum dilution giving absorbance values Ն0.2 and being at least three times the value corresponding to the preimmune serum at the same dilution. Different murine mAbs were used in the study as controls: ior-CEA1 (IgG1, , anti-carcinoembryonic Ag), ior-C5 (IgG1, ) against a glycoprotein expressed on human colorectal cells, and 14F7 (IgG1, ) anti-NeuGc-GM 3 (27)(28)(29).…”

Section: Ab Binding Assaysmentioning

confidence: 99%

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Alfonso

Diaz

Hernández

et al. 2002

The Journal of Immunology

113

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We generated the 1E10 γ-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM3 ganglioside.

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Characterization of the Colorectal Antigen IOR-C2

Cited by 17 publications

References 20 publications

Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity

Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity

Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell lung cancer: Report of a phase I trial

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

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