γδ T cells for immune therapy of patients with lymphoid malignancies

Wilhelm, Martin; Kunzmann, Volker; Eckstein, Susanne; Reimer, Peter; Weißinger, Florian; Rüediger, Thomas; Tony, Hans‐Peter

doi:10.1182/blood-2002-12-3665

Cited by 491 publications

(552 citation statements)

References 33 publications

(33 reference statements)

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“…Toxicity in the patients was moderate, including a transient flu-like syndrome 3 days after the first administration of zoledronate/ IL-2 (67% of subjects) or zoledronate alone (22%), as reported earlier for multiple myeloma and NHL patients. 32 A significant clinical response, including higher survival, was observed in group B during the 1-year follow-up. In addition, this outcome correlated with greater numbers of blood cd T cells and with increased rates of effector memory TCRVc9Vd2 1 T cells (i.e., cd cells producing IFN-c, perforin and TNF-related apoptosis-inducing ligand (TRAIL)).…”

Section: Rationale For Harnessing CD Cells In Cancer Immunotherapymentioning

confidence: 82%

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What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

et al. 2012

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During the last several years, research has produced a significant amount of knowledge concerning the characteristics of human cd T lymphocytes. Findings regarding the immune functions of these cells, particularly their natural killer cell-like lytic activity against tumor cells, have raised expectations for the therapeutic applications of these cells for cancer. Pharmaceutical companies have produced selective agonists for these lymphocytes, and several teams have launched clinical trials of cd T cell-based cancer therapies. The findings from these studies include hematological malignancies (follicular lymphoma, multiple myeloma, acute and chronic myeloid leukemia), as well as solid tumors (renal cell, breast and prostate carcinomas), consisting of samples from more than 250 patients from Europe, Japan and the United States. The results of these pioneering studies are now available, and this short review summarizes the lessons learned and the role of cd T cell-based strategies in the current landscape of cancer immunotherapies.

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Section: Rationale For Harnessing CD Cells In Cancer Immunotherapymentioning

confidence: 82%

“…32 The first group (10 patients) received pamidronate (90 mg/3 h intravenous (i.v.) on day 1), followed by IL-2 (from day 3 to day 8 by continuous 24-h i.v.…”

Section: Rationale For Harnessing CD Cells In Cancer Immunotherapymentioning

confidence: 99%

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

et al. 2012

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“…5 Human gd T cells can infiltrate tumors and infected tissues, and their expansion in blood correlates with better clinical outcome in both malignancies and infectious diseases. 6,7 Notably, they can also regulate ab T cells 8,9 and maintain tissue integrity. 10 In vitro, human gd T cells can kill transformed cells, infected cells, and microorganisms.…”

Section: Introductionmentioning

confidence: 99%

TCR-dependent sensitization of human γδ T cells to non-myeloid IL-18 in cytomegalovirus and tumor stress surveillance

et al. 2015

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“…c9d2T cells belong to the major subset of cdT cells in peripheral blood, and are regarded as a potential candidate for tumor immunotherapy because this subset has been shown to display strong antitumor activity against different type of cancer cells. [16][17][18][19][20] However, the low frequency of c9d2T cells in peripheral blood greatly limits their potential clinical applications. c9d2T cells account for only 2-5% of the total peripheral blood T-cell repertoire.…”

Section: Introductionmentioning

confidence: 99%

CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

Zhao

Cui

et al. 2011

Cell Mol Immunol

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Adoptive cell-transfer therapy (ACT) has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, c9d2T cells can be activated and expanded in vitro and in vivo and display strong antitumor activity against colorectal, lung, prostate, ovarian and renal cell carcinomas. However, it is difficult to obtain a large enough number of cdT cells to meet the need for immunotherapy that can overcome the cancer patients' immune suppressive tumor microenvironment. In previous studies, our lab confirmed that c9d2T cells recognized tumor cells via the CDR3d region of the cd-T-cell receptor (TCR). We constructed full-length human peripheral blood mononuclear cell (PBMC)-derived c9 and d2 chains in which the CDR3 region was replaced by an ovarian epithelial carcinoma (OEC)-derived CDR3. We transferred the CDR3d-grafted c9d2TCR into peripheral blood lymphocytes (PBLs) to develop genetically modified c9d2T cells. In vitro studies have shown that these CDR3d-grafted c9d2T cells can produce cytokines after stimulation with tumor cell extracts and exhibit cytotoxicity towards tumor cells, including human OEC and cervical adenocarcinoma. CDR3d-grafted c9d2T cells adoptively transferred into nude mice bearing a human OEC cell line demonstrated significant antitumor effects. These results indicate that CDR3d-grafted c9d2T cells might be candidates for clinical tumor immunotherapy.

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γδ T cells for immune therapy of patients with lymphoid malignancies

Abstract: There is increasing evidence that ␥␦ T cells have potent innate antitumor activity. We described previously that synthetic aminobisphosphonates are potent ␥␦ T cell stimulatory compounds that induce cytokine secretion (ie, interferon ␥

Cited by 491 publications

References 33 publications

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

What lessons can be learned from γδ T cell-based cancer immunotherapy trials?

TCR-dependent sensitization of human γδ T cells to non-myeloid IL-18 in cytomegalovirus and tumor stress surveillance

CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

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