Therapy of Peritoneal Carcinomatosis of Human Colon Cancer Xenografts With Yttrium 90—Labeled Anti—Carcinoembryonic Antigen Antibody ZCE025

Hyams, David M.; Esteban, José M.; Lollo, Charles P.; Beatty, Barbara; Beatty, J. David

doi:10.1001/archsurg.1987.01400230121021

Cited by 17 publications

(2 citation statements)

References 14 publications

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“…Especially against colorectal cancer and ovarian cancer, a number of attractive MoAbs have been developed that have been evaluated in peritoneal carcinomatosis (human) tumor models in nude mice [125][126][127][128] and in phase I -11 clinical studies in man [129][130][131][132]. The advantage of radioim munotherapy is that it circumvents to a large degree the problem of antigen heterogeneity of the tumor and the need for internalization as the irradiation by isotopes may penetrate several layers of cells.…”

Section: Radioiinniunotherapymentioning

confidence: 99%

Intraperitoneal Chemotherapy and Immunotherapy

Eggermont¹,

Sugarbaker

1991

Oncol Res Treat

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The major goal of intraperitoneal (i.p.) cancer treatment is the generation of optimal concentrations of antitumor agents at the site of the tumor. Maximal local antitumor effects must be attained with minimal systemic levels of the anticancer agents. This is true for both regional chemotherapy and regional immunotherapy. Intraperitoneal chemotherapy has been used, with limited success for about 30 years. This mode of therapy is complex and the modest results are probably largely due to procedure associated problems and the fact that it has been applied mostly in a setting with a large tumor burden. The ideal moment to apply i.p. therapy may well be in the adjuvant setting, immediately after resection of the primary tumor in ovarian or gastrointestinal cancer. In this way, most problems associated with i.p. therapy after debulking for recurrent disease such as tumor load, adhesions, unequal distribution of the drug, drug resistance and subperitoneal disease can be circumvented, and no extra surgical procedures for the placement of the catheter will be required.

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Section: Radioiinniunotherapymentioning

confidence: 99%

Intraperitoneal Chemotherapy and Immunotherapy

Eggermont¹,

Sugarbaker

1991

Oncol Res Treat

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“…It is found in tissues of fetuses and, in small amounts, in normal adult tissues and plasma [25]. The reappearence of large amounts of CEA in carcinomas of the colon and its metastases, in carcinomas of the breast, bladder and lung [11,20] has led to the suggestion that radio-labelled antibodies against CEA should be used for localizing CEA-containing tumours [18,23,24] and maybe also for the targeting of cytotoxic radionuclides such as 131I [5,32,39] or 90y [21,33]. It has, with immuno-histochemical methods, been shown that the CEA expression in human colon carcinomas might be extremely heterogeneous [13].…”

Section: Introductionmentioning

confidence: 99%

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids

Carlsson

Daniel-Szolgay

Frykholm

et al. 1989

Cancer Immunol Immunother

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The monoclonal antibodies 38S1, directed against the carcinoembryonic antigen (CEA), were tested for penetration and binding in human colon carcinoma HT-29 spheroids. Penetration was studied with a method which has not previously been used in immunological investigations. The method, which allows unbound substances to be visualized, is based on freeze drying, vapour fixation, dry sectioning and dry autoradiography. The antibodies penetrated easily and all parts of the HT-29 spheroids seemed to be reached within 15 min. The penetration was even faster than in control glioma U-118MG spheroids that did not express CEA. Binding of the 38S1 antibodies was demonstrated after processing with conventional histology and autoradiography. The binding in the HT-29 spheroids was, after a 1-h incubation period, extremely heterogeneous and occurred mainly in the peripheral parts. More cells were binding the antibodies after 8-h and 32-h incubations and these cells were arranged in peripheral clusters. No binding at all was seen in the CEA-negative glioma spheroids. The distribution of CEA antigens in monolayers and in frozen sections of spheroids of HT-29 cells was analysed with immunohistochemical staining using polyclonal CEA antibodies. The CEA antigens were heterogeneously distributed in both spheroids and monolayers and were as heterogenous as the binding of the monoclonal antibodies in the living spheroids. Thus, the heterogeneous binding in the living spheroids was not due to penetration barriers, but instead to the heterogeneity in the CEA antigen expression.

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