Ex vivo expansion of non-MHC-restricted cytotoxic effector cells as adoptive immunotherapy for myeloma

Wu, Jillian; Ernstoff, Marc S.; Hill, John M.; Cole, Bernard F.; Meehan, Kenneth R.

doi:10.1080/14653240600620218

Cited by 16 publications

(23 citation statements)

References 28 publications

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“…Blocking the NKG2D receptor prevented myeloma cell killing. (17) More importantly, we show that NKG2D + CD8 + T cells derived from patients with myeloma recognize and kill autologous myeloma cells. (16).…”

Section: Discussionmentioning

confidence: 80%

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Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma

Talebian¹

2009

Front Biosci

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The immune system plays a critical role determining the outcomes in transplanted multiple myeloma patients, since enhanced lymphocyte recovery results in improved survival. Since mobilization regimens influence the cellular subsets collected and infused for transplant, these regimens may determine immune recovery following transplant. We hypothesized that a mobilized stem cell product harboring an increased number of lymphocytes would enhance immune recovery following autologous stem cell infusion, increase lymphocyte recovery, and improve clinical outcomes. We designed a phase I immune mobilization trial using IL-2 and growth factors to increase the number of lymphocytes within the stem cell product. This regimen efficiently mobilized CD34+ progenitor cells (median: 3.6 × 106 cells/kg; range 1.9–6.6 × 106 cells/kg) and improved the immune properties of the mobilized stem cells, including an increase in CD8+ T cells expressing an NK activating receptor called NKG2D (P< 0.004), cells that are extremely potent at killing myeloma cells using non-MHC-I restricted and TCR-independent mechanisms. Novel mobilization techniques can improve the mobilized graft and may improve clinical outcomes in myeloma patients.

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Section: Discussionmentioning

confidence: 80%

“…(23–26) NKG2D ligands are upregulated on most tumor cells, but not on healthy cells. (17, 23) (24) (27, 28) Animal studies further support NKG2D-mediated recognition and tumor lysis. Mice bearing tumors that express very low levels of NKG2D ligands develop aggressive disease since these malignant cells escape immune surveillance.…”

Section: Discussionmentioning

confidence: 84%

Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma

Talebian¹

2009

Front Biosci

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“…Several approaches have been used to augment the immunological response to malignancies by the stimulation of lymphocytes or other inflammatory cells, such as cytotoxic T-cells [3][4][5][6][7], macrophages [8], tumor-infiltrating lymphocytes [9,10], and dendritic cells [11][12][13][14][15]. However, despite recent improvements, it has little therapeutic effect when applied clinically for the treatment of cancers, because most of the malignancies lack tumor-associated antigens which are recognized by T-lymphocytes through major histocompatibility complex (MHC) molecules, and seem to evade host immunological defense [1,16].…”

Section: Introductionmentioning

confidence: 99%

Induction of Antitumor Response by In Vivo Allogeneic Major Histocompatibility Complex Gene Transfer Using Electroporation

Shimizu

Nukui

Mitsuhashi

et al. 2009

Journal of Surgical Research

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“…For example, the combination of nutrients, lipids, prostaglandins, trace elements and amino acid composition can significantly affect culture outcomes such as the ability of APC to present Ag [113,114], the T cells to recognize, proliferate and secrete cytokines in response to the Ag [115], or the final phenotype of cells resulting from culture in the media [116]. Two of the more frequently used media for ex vivo culture of T cells include X-VIVO15 and AIM-V [94,96,109,111,116]. Both of these media support 10 3 -10 4 -fold expansion of T cells, including both CD4 + and CD8 + cells with functional attributes (cell killing and T H 1 cytokine production).…”

Section: Media and Cytokinesmentioning

confidence: 99%

“…insulin and transferrin) to serum-free or chemically defined media. Not all media perform equally, and a screening process is often utilized to determine which media is optimal for the culture of T cells for a particular application [96,[109][110][111][112]. Quite often the criteria used to screen media include proliferation and viability of cells.…”

Section: Media and Cytokinesmentioning

confidence: 99%

Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

DiGiusto

Cooper

2007

Cytotherapy

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The production of clinical-grade T cells for adoptive immunotherapy has evolved from the ex vivo numerical expansion of tumor-infiltrating lymphocytes to sophisticated bioengineering processes often requiring cell selection, genetic modification and other extensive tissue culture manipulations, to produce desired cells with improved therapeutic potential. Advancements in understanding the biology of lymphocyte signaling, activation, homing and sustained in vivo proliferative potential have redefined the strategies used to produce T cells suitable for clinical investigation. When combined with new technical methods in cell processing and culturing, the therapeutic potential of T cells manufactured in academic centers has improved dramatically. Paralleling these technical achievements in cell manufacturing is the development of broadly applied regulatory standards that define the requirements for the clinical implementation of cell products with ever-increasing complexity. In concert with academic facilities operating in compliance with current good manufacturing practice, the prescribing physician can now infuse T cells with a highly selected or endowed phenotype that has been uniformly manufactured according to standard operating procedures and that meets federal guidelines for quality of investigational cell products. In this review we address salient issues related to the technical, immunologic, practical and regulatory aspects of manufacturing these advanced T-cell products for clinical use.

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Ex vivo expansion of non-MHC-restricted cytotoxic effector cells as adoptive immunotherapy for myeloma

Cited by 16 publications

References 28 publications

Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma

Novel mobilization strategies to enhance autologous immune effector cells in multiple myeloma

Induction of Antitumor Response by In Vivo Allogeneic Major Histocompatibility Complex Gene Transfer Using Electroporation

Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

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