Zoledronate-activated Vγ9γδ T cell-based immunotherapy is feasible and restores the impairment of γδ T cells in patients with solid tumors

Noguchi, Atsutaka; Kaneko, Toru; Kamigaki, Takashi; Fujimoto, Katsunada; Ozawa, Masanao; Saito, Masashi; Ariyoshi, Naoko; Goto, Shigenori

doi:10.3109/14653249.2010.515581

Cited by 84 publications

(58 citation statements)

References 13 publications

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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%

“…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. 10 Potential anti-tumour effects have been reported in some patients upon cd T-cell transfer, [8][9][10] even the complete remission of lung metastasis appeared following adoptive immunotherapy with activated autologous cd T cells in a patient with renal cell carcinoma.…”

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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“…Although the tumor response could not be assessed in all patients, six out of the 25 enrolled showed disease stabilization. 44 Non-small cell lung cancer cells are also recognized and killed by human TCRVc9Vd2 1 cd T cell; therefore, 10 non-small cell lung cancer patients were enrolled to receive autologous cd T-cell immunotherapy 3-12 times, every 2 weeks. One serious adverse event (grade 3 pneumonia) was recorded, and neither a complete response nor stabilization was observed.…”

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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“…Freshly isolated and expanded γδ T cells from the peripheral blood of healthy donors can destroy neuroblastoma cells while adoptive transfer of γδ T cells, expanded under clinical grade conditions, in combination with immunocytokines are effective against disseminated neuroblastoma established in mice (Otto et al, 2005;Schilbach et al, 2000). Recently, a clinical study of 25 patients with advanced stages of various solid tumors demonstrated that γδ T cell based immunotherapy is beneficial and importantly, such a therapy did not induce any serious treatment related side effects (Noguchi et al, 2011). However, these cells comprise a minor fraction (1-5 %) of the peripheral blood lymphocytes and consequently γδ T cell based immunotherapy requires prior expansion ex vivo.…”

Section: γδ T Cellsmentioning

confidence: 99%

“…However, these cells comprise a minor fraction (1-5 %) of the peripheral blood lymphocytes and consequently γδ T cell based immunotherapy requires prior expansion ex vivo. Protocols to expand γδ T cells using therapeutic grade materials have been developed to facilitate the initiation of clinical trials to treat patients with cancer (Noguchi et al, 2011).…”

Section: γδ T Cellsmentioning

confidence: 99%