Expression of Fcμ receptors on human natural killer cells

Pricop, Luminita; Galatiuc, Cecilia; Manciulea, Mioara; DeLeo, Albert B.; Sulica, Andrei; Herberman, Ronald B.; Tl, Whiteside

doi:10.1016/0090-1229(91)90031-5

Cited by 19 publications

(6 citation statements)

References 27 publications

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“…Among the surface molecules involved in signal transduction on NK cells are the FcR CD16, CD32, and the receptor for IgM (36,40,44). The presence on NK cells of the latter two types of FcR has been confirmed recently (36,44).…”

Section: I2mentioning

confidence: 94%

Role of human natural killer cells in health and disease

Herberman

1994

Clin Diagn Lab Immunol

150

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Natural killer (NK) cells, the CD3- CD56+ CD16+ subset of peripheral blood lymphocytes, have long been known to be involved in non-major histocompatibility complex-restricted natural immunity to virally infected and malignant target cells. The association of abnormalities in NK cell numbers or functions with a broad spectrum of human diseases has been more clearly defined in recent years as a result of the improved knowledge of NK cell physiology and advances in monitoring of NK cell functions in health and disease. The ability to reliably measure changes in NK activity and/or numbers during the course of disease or response to treatment has focused attention on the role of the NK cell in disease pathogenesis. The improved understanding of NK cell deficiency in disease has opened a way for therapies specifically designed to improve NK cell function. The therapeutic use of biologic response modifiers capable of augmenting NK cell activity in vivo and of adoptive transfer of highly enriched, activated autologous NK cells in diseases such as cancer and AIDS is being evaluated. The importance of NK cells in health and the consequences of NK cell deficiency or excess are likely to be more extensively monitored in the future.

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Section: I2mentioning

confidence: 94%

Role of human natural killer cells in health and disease

Herberman

1994

Clin Diagn Lab Immunol

150

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“…Fcbt receptors have been described on B lymphocytes, on the helper subset of T lymphocytes, and recently on natural killer (NK) cells, but their functional role remains to be clarified. In NK cells they appear to be important functional molecules, which deliver negative regulatory signals [21].…”

Section: Discussionmentioning

confidence: 99%

Functional properties of FC-2.15, a monoclonal antibody that mediates human complement cytotoxicity against breast cancer cells

Ballaré

Barrio²,

Portela³

et al. 1995

Cancer Immunol Immunother

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FC-2.15 is a murine IgM monoclonal antibody (mAb) that recognizes a cell-surface antigen (Ag2.15) expressed in most tumor-proliferating cells of human breast carcinomas and other neoplasias. In this study the cytotoxic ability of mAb FC-2.15, its cell-surface binding properties and endocytosis in Ag2.15-expressing (Ag2.15+) cells were investigated. A 51Cr-release assay was used to test the FC-2.15-mediated cytotoxicity. When human serum was used as source of complement, FC-2.15 exerted a strong cytotoxic effect against human Ag2.15+ cells such as MCF-7 (breast cancer cell line), primary breast carcinoma cells, polymorphonuclear leukocytes and chronic myeloid leukemia cells. The mAb concentration range was 1-50 micrograms/ml. Cytotoxicity was completely abolished when complement was inactivated. Only 3.8 +/- 2.9% of MCF-7 cells survived the treatment with FC-2.15 in the presence of human serum. A flow-cytometry assay was performed to study the Ag2.15 expression of the surviving cells and they were found to be Ag2.15-. FC-2.15 did not mediate antibody-dependent cell cytotoxicity when different effector cells were used. Scatchard analysis with 125I-FC-2.15 on MCF-7 cells demonstrated an affinity constant of 6.9 x 10(7) M-1 and 2.8 x 10(6) antigenic sites/cell. 125I-FC-2.15 was internalized to cytoplasmic vesicles reaching a maximum of 27% after 6 h incubation, followed by the release of labeled degradation products to the supernatant. FC-2.15 appears to exert its cytotoxic effect mainly in the presence of human complement, it reacts with intermediate affinity with a high-density surface antigen, and it is slowly internalized by Ag2.15+ cells.

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“…The BN/GRP receptor antagonist [D-Trp6, Leu13-i/f (CH2NH)Phe14]BN (6)(7)(8)(9)(10)(11)(12)(13)(14) was reported by Radulovic et al. to be particularly effective in inhibiting the growth of Swiss 3T3 cells and H345 cells (7).…”

Section: Synthesis Of Grp Antagonistmentioning

confidence: 97%

“…monoclonal antibody (mAb) to GRP in SCCL patients FcyRIII is expressed on natural killer (NK) cells and large granular lymphocytes. Both FcyRI and FcyRIII function as cytotoxic trigger molecules when engaged by a ligand (11,12). MATERIALS (14), was produced in this laboratory.…”

Section: Introductionmentioning

confidence: 99%

Lysis of Small Cell Carcinoma of the Lung (SCCL) Cells by Cytokine-Activated Monocytes and Natural Killer Cells in the Presence of Bispecific Immunoconjugates Containing a Gastrin-Releasing Peptide (GRP) Analog or a GRP Antagonist

Chen¹,

Zhou²,

Mokotoff³

et al. 1995

Journal of Hematotherapy

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Lung cancer remains the leading cause of cancer deaths in the United States. We have developed a new immunotherapeutic approach to the treatment of small cell carcinoma of the lung (SCCL) by targeting the gastrin-releasing peptide receptor (GRP-R) expressed on the surface of these cells. Bispecific immunoconjugates were constructed by chemical fusion of a GRP analog or a GRP antagonist with monoclonal antibodies directed to the cytotoxic trigger molecules Fc gamma RI and Fc gamma RIII on various immune effector cells. We demonstrated that these bispecific immunoconjugates bound to target SCCL cells in a dose-dependent manner. In the presence of these immunoconjugates, more than 80% of SCCL cells were lysed by cytokine-activated monocytes and natural killer (NK) cells measured by a 51Cr-release assay. These data indicate that bifunctional antibodies targeting GRP may have clinical use.

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Expression of Fcμ receptors on human natural killer cells

Cited by 19 publications

References 27 publications

Role of human natural killer cells in health and disease

Role of human natural killer cells in health and disease

Functional properties of FC-2.15, a monoclonal antibody that mediates human complement cytotoxicity against breast cancer cells

Lysis of Small Cell Carcinoma of the Lung (SCCL) Cells by Cytokine-Activated Monocytes and Natural Killer Cells in the Presence of Bispecific Immunoconjugates Containing a Gastrin-Releasing Peptide (GRP) Analog or a GRP Antagonist

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