Monoclonal antibodies raised against mid‐gut carcinoid tumor cells

Abstract

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.

MHC class I and II antigen expression and interferon α treatment of human midgut carcinoid tumors

“…The 48-hour culture period was associated with no appreciable alteration in reactivity toward the murme monoclonal C6 antibody. This IgG2a antibody was generated after immunization with viable cells from a human midgut carcinoid tumor and seems to recognize a differentiation antigen of hitherto unknown function on the plasma membrane of these lesions [12]. This observation contrasts with analyses of exocrine malignancies, in which IFN treatment has been assor with enhanced expression of tumor-associated antigens [32].…”

“…lmmunohistochemistry Staining was performed on acetone-fixed, 6/xm thick cryosections from all tumor specimens utilizing monoclonal antibodies to human MHC class I (HLA-ABC, diluted 1:100) and class II antigens (HLA-DR, diluted 1:36) (Dakopatts, Glostrup, Den-mark). The murine monoclonal antibody C6 (5 ~g/ml) recognizing human midgut carcinoid tumor cells [12] was used as a positive control, and omission of the MHC-reactive antibodies and substitution with the murine monoclonal anti-parathyroid antibody Ell (5/~g/ml) [13] served as negative controls. Monoclonal antibodies recognizing human CD4 (anti-Leu 3A, diluted 1:16) and CD8 (anti-Leu 2A, diluted 1:40) (Becton Dickinson, Mountain View, CA, USA) was used to identify infiltrating Tlymphocytes.…”

Chronic Refractory Diarrhoea: A Manifestation of Endocrine Disorders

“…Sandostatin, SMS 201-995) is a potent inhibitor of hormone secretion by carcinoid cells [4], Indeed, this agent provides effective control of diarrhoea, flush ing and wheezing in more than 75% of cases of carcinoid syndrome in association with achieving a significant reduction in levels of urinary 5-HIAA. Recently Juhlin et al [12] raised monoclonal antibodies against midgut carcinoid tumour cells and proposed their use in immunotherapy for these neoplasms. It is interesting to note that patients with car cinoid tumour with hepatic metastases may live a long time.…”