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- Alici, E, et al.
(författare)
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Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:6, s. 3155-3162
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)–compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
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- Barkholt, L, et al.
(författare)
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Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study
- 2009
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Ingår i: Immunotherapy. - : Future Medicine Ltd. - 1750-7448 .- 1750-743X. ; 1:5, s. 753-764
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Tidskriftsartikel (refereegranskat)abstract
- The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum α-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
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