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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 12 (1973), S. 990-996 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 9 (1970), S. 5083-5092 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 16 (1977), S. 2902-2908 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Incubation of peripheral blood mononuclear cells with interleukin-2 (IL-2) results in the release of a factor which is cytostatic and cytotoxic both to tumor cell lines (A375M, A375P, C480, MCF-7, Hey) and fresh tumor cells (in the human tumor cloning assay), including breast cancer, colon cancer, melanoma, myeloma and ovarian cancer. The factor cannot be detected in a 4-h chromium-release assay, but is best demonstrated after tumor cells have been to it for exposed 3 days. The factor is not cytotoxic to normal peripheral blood leukocytes or normal fibroblasts, and is not toxic to certain targets sensitive to lymphokine-activated killer (LAK) cells, such as K562 and Daudi cells. The factor is diffusible, non-dialyzable, relatively stable to heat and acid and does not contain appreciable amounts of targets resistant to interferon-α and β, tumor necrosis factor β and interleukin-1. The data suggest that there are several mechanisms of LAK cell activity against tumor cells including one which requires direct interaction of LAK and tumor cells and one which is mediated by LAK cell supernatant. The former is detected by 4-h chromium release while the latter is not.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Keywords: B lymphocytes ; Tumor antibodies ; Tumor-infiltrating lymphocytes ; Immunoglobulin ; Immunoglobulin isotypes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cell suspensions from 69 human tumor biopsies and malignant effusions depleted of infiltrating T cells were incubated for 10–14 days with mitomycin-C-treated cells of the transformed T cell line MOT as feeder cells. B lymphocytes proliferated and differentiated as indicated by immunoglobulin (Ig) seerction in the culture supernatants (B cell expansion). Ig was present in culture supernatants of tumor cell suspensions incubated without MOT feeder cells (non-expanded cells), but the addition of MOT feeder cells to these cultures invariably resulted in a significant increase in Ig concentration. While IgG, IgA. and IgM isotypes were all detected in supernatants of both expanded- and nonexpanded tumor cell suspensions, the increase in total Ig induced by MOT feeder cells was mainly due to an increase in IgG. Peripheral blood B lymphocytes (PBBL) from 15 cancer patients and 4 healthy individuals were also successfully expanded by the same method. In these it was shown that IgA was the predominant Ig isotype. Using a modified enzyme-linked immunosorbent assay, IgG of 25/36 expansions from tumor cell suspensions showed reactivity with autologous tumor targets, and that from 10/13 expansions reacted with allogeneic tumor targets of the same histological diagnosis. No reactivity was found against tumor targets of different histology. IgG of 4/10 expansions of PBBL from cancer patients showed reactivity with allogeneic tumor targets of the same histology, while no reactivity was demonstrated against tumor targets of different histology. IgG of expanded PBBL from healthy individuals showed no reactivity against tumor targets. This method allows detailed study of the specific humoral antitumor immune response of intratumoral and peripheral blood B lymphocytes in cancer.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Keywords: Key words: B lymphocytes – Tumor antibodies – Tumor-infiltrating lymphocytes – Immunoglobulin – Immunoglobulin isotypes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Cell suspensions from 69 human tumor biopsies and malignant effusions depleted of infiltrating T cells were incubated for 10–14 days with mitomycin-C-treated cells of the transformed T cell line MOT as feeder cells. B lymphocytes proliferated and differentiated as indicated by immunoglobulin (Ig) secretion in the culture supernatants (B cell expansion). Ig was present in culture supernatants of tumor cell suspensions incubated without MOT feeder cells (non-expanded cells), but the addition of MOT feeder cells to these cultures invariably resulted in a significant increase in Ig concentration. While IgG, IgA, and IgM isotypes were all detected in supernatants of both expanded- and non-expanded tumor cell suspensions, the increase in total Ig induced by MOT feeder cells was mainly due to an increase in IgG. Peripheral blood B lymphocytes (PBBL) from 15 cancer patients and 4 healthy individuals were also successfully expanded by the same method. In these it was shown that IgA was the predominant Ig isotype. Using a modified enzyme-linked immunosorbent assay, IgG of 25/36 expansions from tumor cell suspensions showed reactivity with autologous tumor targets, and that from 10/13 expansions reacted with allogeneic tumor targets of the same histological diagnosis. No reactivity was found against tumor targets of different histology. IgG of 4/10 expansions of PBBL from cancer patients showed reactivity with allogeneic tumor targets of the same histology, while no reactivity was demonstrated against tumor targets of different histology. IgG of expanded PBBL from healthy individuals showed no reactivity against tumor targets. This method allows detailed study of the specific humoral antitumor immune response of intratumoral and peripheral blood B lymphocytes in cancer.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We recently reported that interleukin-2(IL-2)-activated peripheral blood lymphocytes and CD3+, lymphokine-activated killer (LAK) cell clones release tumor necrosis factor α(TNFα) and interferon γ (IFNγ) when stimulated with K562 erythroleukemia cells. We examined the phenotype of IL-2-activated peripheral blood leukocytes that secrete TNFα and IFNγ when stimulated with K562 cells and demonstrated that TNFα secretion is not due to the presence of contaminating mononuclear phagocytes. Further, we demonstrate that IL-2-activated natural killer (NK) cells release only IFNγ when stimulated with K562 cells while T lymphocytes exposed to monoclonal anti-CD3 and K562 cells secrete both TNFα and IFNγ. However, T cells stimulated only with K562 cells did not release IFNγ or TNFα while the admixture of these T cells with NK cells, when stimulated with K562 cells, released levels of TNFα comparable to those produced by the unseparated cells. At present it is unclear whether only one or both effector cell types respond to K562 by releasing TNFα or why the presence both cell types is needed.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0851
    Keywords: Tumor-infiltrating lymphocytes B lymphocytes ; Tumor necrosis factor ; TNF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating B lymphocytes are found within tumors, where their role and the antigens they recognize are poorly defined. After in vitro expansion of these cells, we were able to detect the production of antibodies to tumor necrosis factor α (TNF) in 13 of 17 human tumors studied. These antibodies were detected by both enzyme-linked immunosorbent assay and by neutralization. Anti-TNF antibodies were not produced by resting peripheral blood B cells of normal subjects. However, anti-TNF antibodies were produced by B cells obtained from healthy individuals, after either in vivo or in vitro antigenic stimulation. This suggests that anti-TNF antibody production may constitute part of the overall B cell response to antigens. The intratumoral production of anti-TNF antibody may play a role in tumor/host interactions.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0851
    Keywords: Key words Tumor-infiltrating lymphocytes ; B lymphocytes ; Tumor necrosis factor ; TNF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating B lymphocytes are found within tumors, where their role and the antigens they recognize are poorly defined. After in vitro expansion of these cells, we were able to detect the production of antibodies to tumor necrosis factor α (TNF) in 13 of 17 human tumors studied. These antibodies were detected by both enzyme-linked immunosorbent assay and by neutralization. Anti-TNF antibodies were not produced by resting peripheral blood B cells of normal subjects. However, anti-TNF antibodies were produced by B cells obtained from healthy individuals, after either in vivo or in vitro antigenic stimulation. This suggests that anti-TNF antibody production may constitute part of the overall B cell response to antigens. The intratumoral production of anti-TNF antibody may play a role in tumor/host interactions.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lymphokine-activated killer (LAK) cells are generated by the culture of peripheral blood lymphocytes with interleukin-2 (IL-2). A variety of cells, including T-lymphocytes and natural killer (NK) cells, can be activated by IL-2 to exhibit the ability to kill multiple tumor and “modified-self” targets. Recent reports indicate that culture conditions can determine the phenotype of cells expressing LAK activity. Using limiting dilution techniques, we first generated cloned LAK cells with three culture conditions: autologous human serum (AHS)+IL-2; AHS+IL-2+0.1 μg/ml phytohemagglutinin and fetal bovine serum and IL-2. We determined that all but one of the 47 LAK cell clones generated with the three culture conditions were CD3+ and T-cell like; one NK-like clone was observed. Clones that were cytotoxic for one target could generally kill multiple targets, and the absence of phytohemagglutinin did not significantly affect the ability of the LAK cell clones to kill multiple targets. The presence of phytohemagglutinin was, however, necessary for the long-term maintenance of proliferation and cytotoxic activity of the LAK cell clones. The mechanism by which LAK cells kill tumor targets is not known. We here demonstrate that LAK cells and LAK cell clones can produce interferon-γ and tumor necrosis factor (TNF) when stimulated with an erythroleukemia cell, K562. Five of the six CD3+, LAK cell clones tested could be stimulated by K562 cells to produce both interferon-γ and TNF. However, the ability of the cloned LAK cells to kill K562 cells, as measured in a 4-h 51Cr-release assay, did not correlate with their ability to produce these cytokines. Furthermore, specific antibodies that neutralize the cytotoxic activity of interferon-γ and TNF did not inhibit killing of K562 cells by LAK cells as measured with a 4-h cytotoxic assay. The cytostatic and cytotoxic activities of interferon-γ and TNF for tumor cells are well documented, but these cytolytic activities are slower acting and exhibit their maximum effect after 48–96 h. We here propose that LAK cells kill tumor targets by a combination of cell-to-cell-mediated killing and by the release of slower acting cytostatic/cytotoxic cytokines that can inhibit the growth of tumors some distance from the effector cells.
    Type of Medium: Electronic Resource
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