Sensitiziation of human lymphocytes to carcinoembryonic antigen (CEA): neutralization experiments with anti-CEA sera

Müller, Martin; Irmscher, J; Heidl, G.; Grossmann, H; Wagner, H; Kotzsch, Matthias; Zotter, Stefan

doi:10.1016/s0232-1513(82)80047-9

Cited by 5 publications

(1 citation statement)

References 9 publications

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“…Because of its limited normal tissue distribution, radiolabeled antibodies against CEA have been studied experimentally and clinically for immunodiagnosis and therapy [19,39,40,50]. Until recently, the evidence for immune responsiveness in humans to CEA was con-¯icting [17,24,26,33]. However, clinical studies with anti-idiotype antibodies [14] and in vitro experiments with peripheral blood lymphocytes from both cancer patients and normal individuals [3,47] have demonstrated that the human T and B cell repertoire can recognize CEA.…”

Section: Introductionmentioning

confidence: 99%

Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen

Mizobata

Tompkins

Simpson

et al. 2000

Cancer Immunol Immunother

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In order to develop immunotherapy strategies that are based on eliciting immune responsiveness to the self-antigen, human carcinoembryonic antigen (CEA), we examined whether cytotoxic T lymphocyte (CTL) activity against CEA could be elicited in CEA-transgenic and nontransgenic mice. CEA-transgenic [C57BL/ 6-TGN(CEAGe)18FJP] and nontransgenic mice were primed with CEA-transfected syngeneic fibroblasts in combination with Corynebacterium parvum. Spleen cells from immunized mice were cultured with irradiated syngeneic MC-38 colon carcinoma cells transfected with CEA (MC-38.CEA) as stimulators prior to the measurement of CTL activity. Primed nontransgenic spleen cells showed augmented CTL activity against MC-38.CEA cells as compared with control parental MC-38 cells, nontransfected or transfected with vector only. Moreover, primed CEA transgenic spleen cells showed augmented CTL activity against MC-38.CEA cells that was similar to that observed in nontransgenic mice. All CTL clones derived from either transgenic or nontransgenic mice showed cross-reactivity with MC-38 cells expressing the CEA-related antigen, nonspecific cross-reacting antigen, but not biliary glycoprotein. CEA-specific CTL clones were not identified. Adoptive transfer of cloned CTL resulted in inhibition of MC-38.CEA but not MC-38.BGP tumor growth. Tumor cures were elicited in mice treated with a combination of cloned CTL and cyclophosphamide. Histopathological examination of CEA-expressing colons from either immunized mice or recipients of cloned CTL did not reveal any autoimmune reactions. These studies demonstrate that CTL recognizing cross-reactive class I epitopes on the CEA molecule can be induced in transgenic mice. The expression of these epitopes on tumor cells creates effective targets for CTL in vivo without inducing adverse reactions in CEA-expressing normal tissues. Since anti-CEA CTL have been generated in humans, CEA-transgenic mice may be a useful model to study vaccines that are based on CTL effector mechanisms.

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Section: Introductionmentioning

confidence: 99%

Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen

Mizobata

Tompkins

Simpson

et al. 2000

Cancer Immunol Immunother

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Immunohistochemical analysis of the relationship between CEA localization and mononuclear cell infiltration in human colorectal carcinoma

Nishimura

Hamada

Yamamura

et al. 1990

Journal of Surgical Oncology

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Thirty cases of colorectal adenocarcinoma were immunohistochemically examined to clarify the relationship between the degree of differentiation of cancer cells reflected by the mode of CEA localization and the infiltration pattern of mononuclear cells in the carcinoma tissues. Leu 1+, Leu 2a+, Leu 3a + 3b+ T lymphocytes, Leu 7+ cells, and IgA-containing plasma cells tended to be distributed more in areas where CEA was localized over the entire surface of the cancer cells or in their surrounding stroma than where CEA was located along the apical surface or within the cytoplasm. Carcinoma cells with the pattern of CEA staining at the former site were previously shown to be less differentiated than those at the latter. There were also CEA-containing phagocytes which were often observed where T cells and IgA plasma cells had aggregated. We speculated that the dedifferentiation of cancer cells might cause the host immune response, especially the cellular immunity, in malignant lesions.

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A human lymphokine released by mononuclear blood cells upon contact with CEA

Müller¹,

Grossmann²,

Wagner³

et al. 1986

Immunology Letters

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Sensitiziation of human lymphocytes to carcinoembryonic antigen (CEA): neutralization experiments with anti-CEA sera

Cited by 5 publications

References 9 publications

Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen

Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen

Immunohistochemical analysis of the relationship between CEA localization and mononuclear cell infiltration in human colorectal carcinoma

A human lymphokine released by mononuclear blood cells upon contact with CEA

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