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  • 1
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous experiments in a syngeneic rat liver tumor model using the colon adenocarcinoma CC531 demonstrated that injection of interleukin-2 (IL-2) induced significant antitumor responses. Furthermore, it was found that this treatment strategy was accompanied by an increase in the number of natural killer (NK) cells in and around the tumor. In the present study, the role of endogenous NK cells in IL-2-mediated antitumor responses was further elucidated by depleting tumor-bearing rats of NK cells, using the anti-CD161A mouse IgG1 antibody 3.2.3. Rats were depleted either after or prior to tumor induction and subsequently treated with IL-2. The results demonstrated that depletion of NK cells in tumor-bearing rats did not influence IL-2-induced antitumor effects. In addition, injection of IL-2 in NK-cell-depleted rats induced repopulation of NK cells in the peripheral blood from 3 days on and further after the last injection with IL-2. Therefore, the possibility cannot be excluded that de novo recruited NK cells play a role in attaining IL-2 mediated antitumor effects, but NK cells, which were present before or during the start of IL-2 therapy, were not relevant.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7276
    Keywords: colon cancer ; immunotherapy ; matrix proteins ; metastasis ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The colon adenocarcinoma cell line CC531 was adopted as a model for immunotherapeutical treatment of experimental colorectal metastases in a syngeneic rat model. We studied the presence and localization of T and natural killer cells, vessels and matrix proteins in in vivo growing CC531 tumours by immunohistochemistry. CC531 tumours were induced either in the lungs by injecting CC531 tumour cells into a tail vein or in the liver by injection of CC531 tumour cells under the liver capsule or into a mesenteric vein. All 3 tumour types were composed of islets of tightly apposed tumour cells surrounded by abundantly present tumour-stroma which contained tumour vessels and matrix proteins. Some of these matrix proteins, especially laminin and collagen IV formed a basal membrane-like structure around the tumour nodules. This structure was most pronounced in mesenteric vein-induced liver tumours and less prominent in subcapsular-induced liver tumours and tail vein-induced lung tumours. Tumour-infiltrating lymphocytes of both T and natural killer cell origin were found in the tumours, but predominantly in the tumour stroma, separated from the islets of tumour cells by the basal membrane-like structure. We hypothesize that the matrix proteins of these tumours play an ambivalent role: they may provide a substratum for migration of effector cells into the tumour stroma but may also provide a barrier preventing direct contact between tumour target cells and immune effector cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7276
    Keywords: colon tumour ; monoclonal antibody ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this paper we describe 4 new monoclonal antibodies to be applied in rat models for cancer. The monoclonal antibodies were obtained by immunizing Balb/c mice with CC531 rat colon adenocarcinoma cells. Hybridomas were produced and 4 were selected for their reactivity with CC531 in vitro (MG1, 2, 3 and 4). All 4 antibodies recognized other rat tumour cell lines and showed limited cross-reactivity with normal rat tissues. Intraperitoneally injected MG1, 2 and 4 homed to in vivo growing, artificially induced CC531 liver metastases. In these in vivo experiments, limited cross-reactivity with normal rat tissues, predominantly of the gastro-intestinal tract, was found. MG4 was found to enhance lysis of CC531 tumour cells mediated by IL-2 activated, cultured natural killer cells. These antibodies are potentially useful for antibody-based laboratory techniques and for investigation of antibody-based immunotherapy of cancer in a rat model.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-6865
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in syngeneic immunocompetent animals. Our data suggest the usefulness of the rat as a test model for vaccines against human cancers overexpressing the CaMBr1 antigen.
    Type of Medium: Electronic Resource
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