<i>In vivo</i> manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients

Meraviglia, Serena; Eberl, Matthias; Vermijlen, David; Todaro, Matilde; Buccheri, Simona; Cicero, Giuseppe; Mendola, Carmela La; Guggino, Giuliana; D’Asaro, Matilde; Orlando, Valentina; Scarpa, Francesco; Roberts, Andrew; Caccamo, Nadia; Stassi, Giorgio; Dieli, Francesco; Hayday, Adrian

doi:10.1111/j.1365-2249.2010.04167.x

Cited by 261 publications

(222 citation statements)

References 43 publications

(72 reference statements)

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“…24 Currently, most clinical studies are aimed at increasing the cd T cell population in patients by administering certain phosphoantigens intravenously to expand cd T cells in vivo, or by adoptive transfer of self cd T cells stimulated with phosphoantigen in vitro. [6][7][8][9][10][11] We have previously established conditions for expanding peripheral blood cd T cells with immobilized anti-cd TCR antibodies over a 2-week culture period. 16 The in vitro-expanded cd T cells displayed potent cytotoxicity against various tumours.…”

Section: Discussionmentioning

confidence: 99%

“…6 In another clinical trial, in patients with advanced breast cancer treated with zoledronate and IL-2, a statistically significant correlation between clinical outcome and peripheral Vc9Vd2 T cell numbers emerged. 7 In addition, the direct transfer of in vitro-expanded cd T cells has been used in some clinical trials and was proven to be safe. [8][9][10] In a trial of adoptive transfer of in vitroexpanded cd T cells to non-small cell lung cancer patients, immunomonitoring data showed that the number of peripheral cd T cells gradually increased with increasing numbers of infusions.…”

Section: Introductionmentioning

confidence: 99%

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Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

et al. 2011

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Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments. cd T cells, which have major histocompatibility complex (MHC)-unrestricted lytic activity, have become a promising candidate population for adoptive cell transfer therapy. We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor (TCR) antibody. In this study, we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status. We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies. Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody. Compared to phosphoantigen-stimulated cd T cells, the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines. It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells. The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells. Importantly, owing to higher C-C chemokine receptor 4 (CCR4) and CCR8 expression, the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells. Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

et al. 2011

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“…Naturally, local access to inflamed tissues and draining lymph nodes in humans is very limited, thereby severely compromising investigations into the APC function of Vc9/Vd2 T cells -or, as a matter of fact, into the APC function of any human immune cell. Indirect support for a possible role as APC stems from observations that HLA-DR is expressed by activated Vc9/Vd2 T cells in patients with severe inflammation or during acute infection [123,[138][139][140], and in patients receiving intravenous zoledronate with and without IL-2 [65,141,142]. However, functional evidence into the potential of activated Vc9/Vd2 T cells to act as APC ex vivo is only beginning to emerge [123,143].…”

Section: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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“…With results from three cd cell-responsive patients reaching either disease stabilization (two patients) or partial remission (one patient), the authors could correlate the clinical outcomes to blood cd T-cell numbers. 37 In France, using the synthetic phosphoantigen BrHPP (IPH1101), Bennouna and colleagues 38 conducted a phase I trial in 28 patients with solid tumors to determine the maximum-tolerated dose and safety of this drug when combined with low doses of IL-2. Patients received BrHPP alone (1 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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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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In vivo manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients

Cited by 261 publications

References 43 publications

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

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

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