Dataset Information

Activating and propagating polyclonal gamma delta T cells with broad specificity for malignancies.

ABSTRACT:

Purpose

To activate and propagate populations of γδ T cells expressing polyclonal repertoire of γ and δ T-cell receptor (TCR) chains for adoptive immunotherapy of cancer, which has yet to be achieved.

Experimental design

Clinical-grade artificial antigen-presenting cells (aAPC) derived from K562 tumor cells were used as irradiated feeders to activate and expand human γδ T cells to clinical scale. These cells were tested for proliferation, TCR expression, memory phenotype, cytokine secretion, and tumor killing.

Results

γδ T-cell proliferation was dependent upon CD137L expression on aAPC and addition of exogenous IL2 and IL21. Propagated γδ T cells were polyclonal as they expressed TRDV1, TRDV2-2, TRDV3, TRDV5, TRDV7, and TRDV8 with TRGV2, TRGV3F, TRGV7, TRGV8, TRGV9*A1, TRGV10*A1, and TRGV11 TCR chains. IFNγ production by Vδ1, Vδ2, and Vδ1(neg)Vδ2(neg) subsets was inhibited by pan-TCRγδ antibody when added to cocultures of polyclonal γδ T cells and tumor cell lines. Polyclonal γδ T cells killed acute and chronic leukemia, colon, pancreatic, and ovarian cancer cell lines, but not healthy autologous or allogeneic normal B cells. Blocking antibodies demonstrated that polyclonal γδ T cells mediated tumor cell lysis through combination of DNAM1, NKG2D, and TCRγδ. The adoptive transfer of activated and propagated γδ T cells expressing polyclonal versus defined Vδ TCR chains imparted a hierarchy (polyclonal>Vδ1>Vδ1(neg)Vδ2(neg)>Vδ2) of survival of mice with ovarian cancer xenografts.

Conclusions

Polyclonal γδ T cells can be activated and propagated with clinical-grade aAPCs and demonstrate broad antitumor activities, which will facilitate the implementation of γδ T-cell cancer immunotherapies in humans.

SUBMITTER: Deniger DC

PROVIDER: S-EPMC4233015 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Activating and propagating polyclonal gamma delta T cells with broad specificity for malignancies.

Deniger Drew C DC Maiti Sourindra N SN Mi Tiejuan T Switzer Kirsten C KC Ramachandran Vijaya V Hurton Lenka V LV Ang Sonny S Olivares Simon S Rabinovich Brian A BA Huls M Helen MH Lee Dean A DA Bast Robert C RC Champlin Richard E RE Cooper Laurence J N LJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20140515 22

<h4>Purpose</h4>To activate and propagate populations of γδ T cells expressing polyclonal repertoire of γ and δ T-cell receptor (TCR) chains for adoptive immunotherapy of cancer, which has yet to be achieved.<h4>Experimental design</h4>Clinical-grade artificial antigen-presenting cells (aAPC) derived from K562 tumor cells were used as irradiated feeders to activate and expand human γδ T cells to clinical scale. These cells were tested for proliferation, TCR expression, memory phenotype, cytokine ...[more]

PMID: 24833662

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Dataset Information

Activating and propagating polyclonal gamma delta T cells with broad specificity for malignancies.

Purpose

Experimental design

Results

Conclusions

Publications

Activating and propagating polyclonal gamma delta T cells with broad specificity for malignancies.

Similar Datasets

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