Physical Connections between Feeder Cells and Recipient Normal Mammary Epithelial Cells

Ehmann, Ursula K.; Stevenson, Mary Ann; Calderwood, Stuart K.; DeVries, James T.

doi:10.1006/excr.1998.4054

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…In this study, we developed an improved method for large-scale expansion of NK cells using an anti-CD16 mAb and irradiated autologous PBMCs as feeder cells instead of cancer cell-based feeder cells. Feeder cells provide a suitable environment for the NK cell expansion through various mechanisms, including direct cell-to-cell interactions and production of soluble growth factors 31 , 32 . CD16 (FcγRIII) is associated with the immunoreceptor tyrosine-based activation motif (ITAM)-containing FcεRI γ chain and CD3ξ chain 33 .…”

Section: Discussionmentioning

confidence: 99%

Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Lee

Son

Koh

et al. 2017

Sci Rep

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Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion. This method more potently expanded NK cells, and the final product was composed of highly purified NK cells with lesser T-cell contamination. The expanded NK cells showed greater upregulation of various activation receptors, CD107a, and secreted larger amounts of interferon gamma. IrAPs expressed NKG2D ligands and CD48, and coengagement of CD16 with NKG2D and 2B4 caused potent NK cell activation and proliferation. The expanded NK cells were cytotoxic toward various cancer cells in vitro and in vivo. Moreover, irradiation or a chemotherapeutic drug further enhanced this antitumor effect. Therefore, we developed an effective in vitro culture method for large-scale expansion of highly purified cytotoxic NK cells with potent antitumor activity using IrAPs instead of cancer cell-based feeder cells.

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Section: Discussionmentioning

confidence: 99%

Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Lee

Son

Koh

et al. 2017

Sci Rep

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“…Decreasing cell spreading appears to inhibit proliferative signals and may mask positive signals from cell‐cell contact: Round cells with maximal contact (representing ‘confluent’ cells) still proliferate much less than spread cells with no contacts (representing ‘sparse’ cells). In the geometry of feeder layer‐dependent cultures, which allows for contact‐mediated signaling without constraining cell spreading, contact has been shown to improve proliferation of various cell types [12,13]. Thus, ‘contact inhibition’ of growth of cells cultured in monolayers may be less a result of cell‐cell contact and more a result of the decreased spreading as cells become crowded.…”

Section: Discussionmentioning

confidence: 99%

Cell‐cell signaling by direct contact increases cell proliferation via a PI3K‐dependent signal

2002

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We report a novel mechanism of cellular growth control. Increasing the density of endothelial or smooth muscle cells in culture increased cell-cell contact and decreased cell spreading, leading to growth arrest. Using a new method to independently control cell-cell contact and cell spreading, we found that introducing cell-cell contact positively regulates proliferation, but that contact-mediated proliferation can be masked by changes in cell spreading: Round cells with many contacts proliferated less than spread cells with none. Physically blocking cell-cell contact or inhibiting PI3K signaling abrogated cell-cell induced proliferation, but inhibiting diffusible paracrine signaling did not. Thus, direct cell-cell contact induces proliferation in these cells. ß

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“…In this study, we used an improved method for activation and expansion of NK cells at present of an anti-CD3 mAb and irradiated autologous PBMCs as feeder layer, for immune cell therapy of HCC. Feeder cells provide a suitable environment for expansion of NK cells through production of soluble growth factors and direct cell-to-cell interactions (Ehmann et al, 1998). In the next step, we examined the cytotoxicity of expanded NK cells (eNKC) against HCC cells and compared with that of fresh isolated NK cells (iNKC).…”

Section: Discussionmentioning

confidence: 99%

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma

Hosseinzadeh

Ebrahimi‐Barough

et al. 2019

Asian Pac J Cancer Prev

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Background: one of the promising approaches for treatment of some cancers is adoptive cell therapy using natural killer (NK) cells. Various methods have been investigated for ex vivo expansion of NK cells in large-scale, but most of them involved cancer or genetically modified cells as feeder layer and also some of them have the risk of T cell contamination and graft-versus-host disease (GVHD). Method: In this study, irradiated autologous peripheral blood mononuclear cells (PBMCs) as feeder layer with an anti-CD3 monoclonal antibody (mAb) were used. For activation and expansion of NK cells, human recombinant IL2 and IL15 were used. After co-culturing of expanded NK cells (eNKC) and isolated NK cells (iNKC) with hepatocellular carcinoma (HCC) cells, the viability of eNKC in compared to iNKC were analyzed by CCK-8 assay and degranulation of NK cells after co-culturing was assayed by measuring CD107a expression. Enzyme-Linked Immunosorbent Assay (ELISA) assay was used for the ability of NK cells to secretion of IFN-γ (interferon-γ) and TNF-α (Tumor Necrosis Factor-α) after co-culture with HCC cells. Real Time PCR analysis was used for expression of human Perforin and Granzyme B genes in the NK cells exposed to target HepG2 cells. Result: This method strongly expanded highly purified NK cells with powerful cytotoxicity against HCC cells. The expanded NK cells showed high level of expression of degranulation marker and human Perforin and Granzyme B genes, and also was secreted larger amounts of TNF-α and IFN-γ compared with fresh isolated NK cells. Conclusion: we proposed an effective method for expansion of cytotoxic NK cells using irradiated autologous PBMC as feeder layer for more successful transfer of allogeneic NK cell in immuno cell therapy of HCC.

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Physical Connections between Feeder Cells and Recipient Normal Mammary Epithelial Cells

Cited by 10 publications

References 21 publications

Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Cell‐cell signaling by direct contact increases cell proliferation via a PI3K‐dependent signal

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma

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