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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 31 (1990), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The murine monoclonal antibody (MoAb) IVF7 was produced against tumour cells from a patient with a CD 3+, CD4+, CD8− T-cell chronic lymphatic leukaemia (T-CLL). The MoAb IVF7 showed reactivity with subpopulations of normal peripheral blood lymphocytes (PBL), as well as with a few cell lines of haematopoietic origin. Thirty-six percent of PBL were stained with IVF7. Analysing subpopulations, we found that 80% of NK cells, 25% of T cells, and 10–20% of B cells were positive. The myelomonocytic cell line KG-1 was also stained. The molecular weight of the molecule was 40 kDa under reducing conditions. The antigen was found to be trypsinsensitive.MoAb IVF7 could modulate the antigen from the cell surface. The antibody did not stimulate PBL to DNA synthesis, nor did it significantly lnfluence NK cell-mediaied kilting.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Key words Monoclonal antibodies ; HAMA ; Anti-idiotypic antibodies ; GM-CSF ; Colorectal carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n=76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P〈0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15 μg/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P〈0.05). Moreover, patients with a high ab2 concentration (at least 15 μg/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P=0.01).
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Keywords: Monoclonal antibodies ; GM-CSF ; Colorcetal carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unconjugated monoclonal antibodies (mAb) may induce tumour regression in patients. The mechanisms of action are complex. Antibody-dependent cellular cytotoxicity (ADCC) is considered one of the effector functions. Augmentation of the killing capacity of cytotoxic cells may thus be a way to increase the therapeutic potential of mAb. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has been shown to enhance this function in vitro. Eighteen patients with metastatic colorectal carcinoma received GM-CSF (250 µg m−2 day−1 s.c.) for 10 days and a single infusion of the anti-(colon carcinoma) mAb 17-1A (mouse IgG2A) (400 mg) on day 3 of the cycle. The cycles were repeated once a month four times. Neutrophils, eosinophils, monocytes and lymphocytes increased significantly in a biphasic way. However, at the fourth cycle the rise in white blood cells was significantly lower compared to the preceding courses. ADCC (SW948, a human CRC cell line, + mAb 17-1A) or peripheral blood mononuclear cells (PBMC) was significantly (P 〈0.05) augmented by day 6 of a cycle and then declined gradually and, at the end of a cycle, the ADCC activity had returned to the pretreatment level. The spontaneous cytotoxicity of PBMC against the natural-killer-resistant cell line, SW948, varied in a similar way. During GM-CSF treatment there was also a significant increase in FcRI+ (CD64), FcRII+ (CD32), FcRIII+ (CD16) and CD14+ cells but not of CD56+ cells.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Keywords: Key words: Monoclonal antibodies – Network response – Anti-idiotype antibodies – T cells – Colon carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The antitumor effector functions of unconjugated monoclonal antibodies (mAb) in cancer therapy are not fully understood. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as the corresponding T cells (T2 and T3) has also been proposed to be of therapeutic significance. In this study induction of an immune network cascade in ten patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. After treatment, all ten patients had anti-idiotypic antibodies and anti-anti-idiotypic antibodies with ab1-like binding specificity while only five of ten patients had T cells corresponding to ab3 (T3) as assessed by a proliferation assay (DNA synthesis), and an assay of interferon γ production (ELISPOT) (Enzyme-linked immuno SPOT) in vitro or by a delayed-type hypersensitivity reaction in vivo. Purified T cells from four of the five patients with a positive T3 test responded with DNA synthesis after stimulation using human anti-mAb 17-1A anti-idiotypic monoclonal antibodies. These four patients had a clinical response showing a tumor reduction after therapy, while all six patients lacking a proliferative response failed to show tumor regression. Induction of a cell-mediated immune network cascade might accordingly be an important antitumor effector function of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0851
    Keywords: Key words: CSF  –  Monoclonal antibodies  –  ADCC  –  Mononuclear cells  –  Granulocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Unconjugated monoclonal antibodies (mAb) kill tumor cells in vivo by activating immune functions. One of these is ADCC (antibody-dependent cellular cytotoxicity). The efficacy of mAbs might be augmented if the cytotoxic capacity of the effector cells could be increased. In this study the augmenting effect of granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage(GM)-CSF and macrophage(M)-CSF was analyzed. Effector cells [peripheral blood mononuclear cells (PBMC) or granulocytes] were activated for 4 – 6 h by the respective CSF and assayed in an 18-h Cr51-release assay. Human colorectal, lymphoma, glioma and melanoma cell lines were target cells. Mouse mAbs of different isotypes, as well as chimeric and humanized mAbs, were used. mAbs having the human Fc part of the IgG molecule were the most effective. The killing capacity of PBMC as well as of granulocytes was statistically significantly enhanced when mAbs were added. M-CSF and GM-CSF were the best CSF for augmenting the lytic capacity of PBMC in ADCC. G-CSF had no significant effect on PBMC. Spontaneous cytolysis of PBMC was significantly augmented only by M-CSF. Granulocytes were, in general, significantly less effective than PBMC but may be equally effective killer cells together with mouse or human mAbs of the IgG1 isotype, particularly against melanoma cells. Granulocytes may also be significantly stimulated to increased lytic capacity when activated with G-CSF or GM-CSF. On the basis of the present evaluation, clinical trials in tumor patients are warranted, combining mAbs with GM-CSF or M-CSF. Preference might be given to GM-CSF as this cytokine activates both PBMC and granulocytes.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 37 (1993), S. 264-270 
    ISSN: 1432-0851
    Keywords: Monoclonal antibodies ; Network response ; Anti-idiotype antibodies ; T cells ; Colon carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effector functions of unconjugated monoclonal antibodies in cancer therapy are complex. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as T cell (T2 and T3 respectively) responses have also been proposed to be of clinical importance. In this study induction of an immune network cascade in patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. All patients developed anti-idiotypic antibodies (ab2) of the IgG class after treatment with ab1 and four of nine patients showed induction of mouse Ig reactive T cells [a proliferative response to F(ab′)2 fragments of ab1]. Patients with such a T cell response developed anti-anti-idiotypic antibodies (ab3), while those lacking the T cell reactivity failed to mount an ab3 response. Three of four patients with a T cell response achieved a tumor response to mAb therapy. Thus, all responding patients belonged to the group of individuals developing ab3. Induction of mAb(ab1)-reactive T cells as well as an immune network cascade might be important antitumor effector functions of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0851
    Keywords: Monoclonal antibodies ; Network response ; Anti-idiotype antibodies ; T cells ; Colon carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effector functions of unconjugated monoclonal antibodies (mAb) in cancer therapy are not fully understood. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as the corresponding T cells (T2 and T3) has also been proposed to be of therapeutic significance. In this study induction of an immune network cascade in ten patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. After treatment, all ten patients had anti-idiotypic antibodies and anti-anti-idiotypic antibodies with ab1-like binding specificity while only five of ten patients had T cells corresponding to ab3 (T3) as assessed by a proliferation assay (DNA synthesis), and an assay of interferon γ production (ELISPOT) (Enzyme-linked immuno SPOT) in vitro or by a delayed-type hypersensitivity reaction in vivo. Purified T cells from four of the five patients with a positive T3 test responded with DNA synthesis after stimulation using human anti-mAb 17-1A anti-idiotypic monoclonal antibodies. These four patients had a clinical response showing a tumor reduction after therapy, while all six patients lacking a proliferative response failed to show tumor regression. Induction of a cell-mediated immune network cascade might accordingly be an important anti-tumor effector function of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0851
    Keywords: CSF ; Monoclonal antibodies ; ADCC ; Mononuclear cells ; Granulocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Unconjugated monoclonal antibodies (mAb) kill tumor cells in vivo by activating immune functions. One of these is ADCC (antibody-dependent cellular cytotoxicity). The efficacy of mAbs might be augmented if the cytotoxic capacity of the effector cells could be increased. In this study the augmenting effect of granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage(GM)-CSF and macrophage(M)-CSF was analyzed. Effector cells [peripheral blood mononuclear cells (PBMC) or granulocytes] were activated for 4–6 h by the respective CSF and assayed in an 18-h Cr51-release assay. Human colorectal, lymphoma, glioma and melanoma cell lines were target cells. Mouse mAbs of different isotypes, as well as chimeric and humanized mAbs, were used. mAbs having the human Fc part of the IgG molecule were the most effective. The killing capacity of PBMC as well as of granulocytes was statistically significantly enhanced when mAbs were added. M-CSF and GM-CSF were the best CSF for augmenting the lytic capacity of PBMC in ADCC. G-CSF had no significant effect on PBMC. Spontaneous cytolysis of PBMC was significantly augmented only by M-CSF. Granulocytes were, in general, significantly less effective than PBMC but may be equally effective killer cells together with mouse or human mAbs of the IgG1 isotype, particularly against melanoma cells. Granulocytes may also be significantly stimulated to increased lytic capacity when activated with G-CSF or GM-CSF. On the basis of the present evaluation, clinical trials in tumor patients are warranted, combining mAbs with GM-CSF or M-CSF. Preference might be given to GM-CSF as this cytokine activates both PBMC and granulocytes.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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