Development of a clinical model for ex vivo expansion of multiple populations of effector cells for adoptive cellular therapy

Meehan, Kenneth R.; Wu, Jillian; Ernstoff, Marc S.; Webber, S.; Barber, Amorette; Szczepiórkowski, Zbigniew M.; Sentman, Charles L.

doi:10.1080/14653240701762398

Cited by 20 publications

(24 citation statements)

References 25 publications

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“…37 As PTLs are primary cells with a limited life span, increased concentration of FBS, IL-2, and OKT3 were added during G418 selection. 38 According to the results reported, during the generation of PTLs, it could be better to add irradiated allogeneic PBMC feeder cells or irradiated allogeneic EBV-transformed lymphoblastoid cell line cells. 39 Although Alvarez et al 40 succeeded in applying recombinant adenoviral anti-erbB2 scFv for phase I clinical gene therapy of ovarian carcinoma, there are still some concerns that remained.…”

Section: Discussionmentioning

confidence: 90%

Adoptive Antitumor Immunotherapy In Vitro and In Vivo Using Genetically Activated erbB2-specific T Cells

Wang

Hu²,

Shen³

et al. 2014

Journal of Immunotherapy

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The use of human T lymphocytes genetically modified to express chimeric antigen receptors on their surfaces has emerged as a promising treatment strategy for malignant tumors. We have transfected primary human peripheral T lymphocytes with a recombinant vector carrying DNA fragments encoding anti-erbB2 scFv/Fc/CD28/CD3ζ chimeric antigen receptor using electroporation. Transfected T cells have been demonstrated to express anti-erB2 scFv/Fc on their surface and CD28/CD3ζ intracellularly. These modified T cells were able to specifically bind to erbB2 tumor-associated antigen on target tumor cells. After specific binding, modified T cells were activated to produce high levels of cytokines (not only interferon-γ but also interluekin-2) and mediate lysis of erbB2-positive human tumor cells in an antigen-specific manner. Furthermore, such genetically modified human T cells significantly delayed the growth of subcutaneous erbB2-positive human xenograft tumors after systemic administration. These preclinical studies suggest that human T cells can be modified genetically and redirected to tumors in cancer patients.

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Section: Discussionmentioning

confidence: 90%

Adoptive Antitumor Immunotherapy In Vitro and In Vivo Using Genetically Activated erbB2-specific T Cells

Wang

Hu²,

Shen³

et al. 2014

Journal of Immunotherapy

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“…Adoptive CTL therapy has been used with significant clinical benefit in EBV-associated lymphoproliferative diseases (Haque et al 2007;Heslop et al 2010), myeloma (Rapoport et al 2005) and acute leukaemia (Marjit et al 2007;Warren et al 2010), as well as certain solid tumours. These and other studies (Turin et al 2007;Meehan et al 2008) have demonstrated the feasibility of generating CTL lines or clones to GMP standards (a requirement for adoptive immunotherapy in humans), as well as the safety and therapeutic benefit of the approach. Our data demonstrate the ability of LCL/tumour hybrid cell lines to stimulate antigen-specific CTL in vitro in PBL from both normal individuals and tumour bearing patients, suggesting their potential as reagents for in vitro induction of tumour-specific CTL for adoptive cellular immunotherapy in haematological malignancies.…”

Section: Discussionmentioning

confidence: 95%

Long-lived fusions of human haematological tumour cells and B-lymphoblastoid cells induce tumour antigen-specific cytotoxic T-cell responses in vitro

et al. 2012

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“…A standard chromium release assay was performed at three effector to target ratios (E:T : 100:1, 20:1, and 4:1) as previously described. (15) A myeloma cell line RPMI8226), a leukemia cell line (K562) or patients’ autologous myeloma cells served as targets.…”

Section: Methodsmentioning

confidence: 99%

“…(15) These ex vivo expanded NKG2D + CD8 + T cells were used as effector cells in vitro . Briefly, PBMC were cultured in serum-free AIM V medium (Invitrogen Corp., Carlsbad, CA) for 2 hours at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Cryopreserved PBMC from myeloma patients were isolated, as previously described. (15) The PBMC were then expanded for 7 days using IL-2 (1000IU/ml) and OKT3 (500ng/ml), a process that enriches for NKG2D + CD8 + T cells. First, CD8 + T cells were isolated using a magnet-activated automated cell separation system (AutoMACS, Miltenyi Biotec AG, Bergisch Gladbach, Germany) as per manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

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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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Development of a clinical model for ex vivo expansion of multiple populations of effector cells for adoptive cellular therapy

Cited by 20 publications

References 25 publications

Adoptive Antitumor Immunotherapy In Vitro and In Vivo Using Genetically Activated erbB2-specific T Cells

Adoptive Antitumor Immunotherapy In Vitro and In Vivo Using Genetically Activated erbB2-specific T Cells

Long-lived fusions of human haematological tumour cells and B-lymphoblastoid cells induce tumour antigen-specific cytotoxic T-cell responses in vitro

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

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