Targeting high‐grade B cell lymphoma with CD19‐specific T cells

Lehmann, F.; Maurberger, Anna; Feicht, Samantha; Helm, Florian; Ladinig, Camilla; Kieback, Elisa; Uckert, Wolfgang; Kammertöns, Thomas; Kremmer, Elisabeth; Mautner, Josef; Gerbitz, Armin; Bornkamm, Georg W.

doi:10.1002/ijc.28760

Cited by 1 publication

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“…ACT has multiple advantages over other forms of cancer immunotherapy, and relies on the transfer of ex vivo activated and sometimes gene-engineered T cells, which encounter and act against tumor antigens in patients, mediating tumor regression in variety of cancer such as melanoma [ 5 ], cervical cancer [ 6 ], lymphoma [ 7 ], leukemia [ 8 ], bile duct cancer and neuroblastoma [ 9 ]. There are many ways to enhance and optimize the ACT approach, such as isolating and re-educating tumor infiltrated lymphocytes in IL-2-containing medium, or genetically modifying T cells to express antigen-specific T cell receptors (TCRs).…”

Section: Introductionmentioning

confidence: 99%

Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient

Siddiqui

Erreni²,

Brakel³

et al. 2016

j. immunotherapy cancer

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BackgroundAdoptive T-cell based immunotherapies constitute a promising approach to treat cancer, however, a major problem is to obtain effective and long-lasting anti-tumor responses. Lack of response may be due to insufficient trafficking of specific T cells to tumors. A key requirement for efficient migration of cytotoxic T cells is that they express chemokine receptors that match the chemokines produced by tumor or tumor-associated cells.MethodsIn this study, we investigated whether the in vivo tumor trafficking of activated T cells could be enhanced by the expression of the chemokine receptor CX3CR1. Two human colorectal cancer cell lines were used to set up a xenograft tumor model in immunodeficient mice; the NCI-H630, constitutively expressing the chemokine ligand CX3CL1 (Fractalkine), and the RKO cell line, transduced to express CX3CL1.ResultsHuman primary T cells were transduced with the receptor CX3CR1-eGFP. Upon in vivo adoptive transfer of genetically modified CX3CR1-T cells in mice bearing NCI-H630 tumors, enhanced lymphocyte migration and tumor trafficking were observed, compared to mice receiving Mock-T cells, indicating improved homing ability towards ligand-expressing tumor cells. Furthermore, significant inhibition of tumor growth was found in mice receiving modified CX3CR1-T cells. In contrast, tumors formed by RKO cells transduced with the ligand (RKO-CX3CL1) were not affected, nor more infiltrated upon transfer of CX3CR1-T lymphocytes, likely because high levels of the chemokine were shed by tumor cells in the systemic circulation, thus nullifying the blood-tissue chemokine gradient.ConclusionsThis study demonstrates that ectopic expression of CX3CR1 enhanced the homing of adoptively transferred T cells towards CX3CL1-producing tumors, resulting in increased T cell infiltration in tumor tissues and decreased tumor growth. Our results also establish that a correct chemokine gradient between the systemic circulation and the tumor is an essential requirement in adoptive T-cell based immunotherapy to efficiently recruit T cell effectors at the correct sites.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-016-0125-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%