Irradiated Mononuclear Cells Express Significant
            <i>In Vitro</i>
            Cytotoxic Activity: Promise for
            <i>In Vivo</i>
            Clinical Efficacy of Irradiated Mismatched Donor Lymphocytes Infusion

Tsirigotis, Panagiotis; Resnick, Igor B.; Kapsimalli, Violetta; Dray, Liliane; Psarra, Ekaterini; Samuel, Simcha; Spyridonidis, A.; Konsta, Evi; Vikentiou, Myrofora; Or, Reuven; Slavin, Shimon; Shapira, Michael Y.

doi:10.2217/imt.14.10

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…Cells were infused after day þ30 (avoiding antithymocyte globulin toxicity) and although, the results might deserve further study, immune recovery was observed. Ideas are not scarce and other novel pDLI approaches are being reported, including mononuclear cell irradiation [97] and a phase II trial of infusion preemptive T-cell rapamycin resistant at day þ14 after allo-HCT [98].…”

Section: In Extramedullary Relapsesmentioning

confidence: 99%

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Ortí

Barba

Fox

et al. 2017

Experimental Hematology

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Section: In Extramedullary Relapsesmentioning

confidence: 99%

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Ortí

Barba

Fox

et al. 2017

Experimental Hematology

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“…Lymphocytes do not perish immediately following irradiation; hence, there is no sustained GVHD with a rising proliferation inhibition rate (9,11,12). As a result, the transfusion of irradiated PBMCs has been performed in certain clinical applications for over a decade (9,11,12,25,26). The aim of the present study was to confirm the optimum dose of X-rays, under appropriate conditions, that can reduce the proliferation of lymphocytes while preserving or enhancing their cytotoxic activity, therefore improving the effectiveness of irradiation in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Irradiation of peripheral blood mononuclear cells with 7.5 Gy X-rays prior to donor lymphocyte infusion inhibits proliferation while preserving cytotoxicity, and improves the effectiveness of HSCT in patients with hematological malignancies

et al. 2017

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The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7.5, 10, 15, 25 or 50 Gy, and their proliferative activity was determined using a WST-8 assay kit. The cytotoxic activity of non-irradiated PBMCs and PBMCs irradiated with 7.5 Gy X-rays was tested in the leukemic cell line K562 and its Adriamycin-resistant strain K562A using a lactate dehydrogenase assay. The clinical data of 7 patients who received 7.5 Gy X-ray-irradiated PBMC infusions following autologous HSCT were analyzed. PBMCs irradiated with ≥7.5 Gy X-rays exhibited a complete inhibition of proliferation. PBMCs irradiated with 7.5 Gy X-rays exhibited significantly increased cytotoxic activity towards K562 cells compared with K562A cells (P<0.05). There was no significant difference in cytotoxicity between irradiated and non-irradiated PBMCs, irrespective of the target cell, K562 or K562A (P>0.05). Based on the in vitro data, clinical data from patients who received 7.5 Gy X-ray-irradiated PBMC infusions following HSCT between January 2005 and January 2013 were assessed retrospectively. A total of 7 patients were included in the current study. The majority achieved various degrees of remission following donor lymphocyte infusion (DLI) and none suffered from GVHD. This indicates that 7.5 Gy-irradiated PMBCs have a potential application in DLI for the treatment of patients following HSCT. However, further studies on larger patient cohorts are required to assess the clinical potential of 7.5 Gy-irradiated PBMCs for preserving the GVT effect while avoiding GVHD following HSCT.

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“…К недостаткам данной линии клеток можно отнести тот факт, что они должны быть облучены перед трансфузией, т. к. происходят из линии опухолевых клеток и несут множество генетических аномалий [30]. Многочисленные исследования показали, что клетки NK-92 сохраняют свою цитотоксичность после облучения, но отсутствие пролиферации in vivo приводит к исчезновению введённых клеток уже через 7 дней [31][32][33]. Следовательно, лечение препаратом CAR на основе NK-92, скорее всего, потребует нескольких циклов трансфузии [32].…”

Section: источники Car Nk-клетокunclassified

Sources of NK Cells for CAR-Technologies

Грибкова,

Завьялов

2023

Voprosy onkologii

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В последние годы клеточная терапия представляется многообещающим подходом к лечению гемобластозов, показывая поразительные результаты в различных клинических исследованиях. Особенные надежды возлагаются на CAR-клетки — клетки с химерными антигенными рецепторами. Наиболее изученной и показавшей значимые клинические результаты является терапия CAR Т-лимфоцитами. Однако существенными проблемами остаются сложности производства CAR Т-клеток из аутологичных материалов и наличие серьезных побочных эффектов при лечении данным методом. Альтернативой применения Т-клеток может стать использование натуральных киллеров (NK-клеток) — клеток врожденного иммунитета, обладающих противоопухолевыми свойствами. Терапия CAR NK-клетками может оказаться более привлекательной, чем терапия CAR Т-клетками, вследствие меньшей токсичности и возможности использования аллогенных материалов. Однако данный метод только развивается и сопряжен со сложностями производства достаточного для инфузии количества CAR NK-клеток, обладающих противоопухолевой активностью, и их модификации. Для преодоления этих проблем используют NK-клетки, полученные из различных источников, подвергая их разнообразным воздействиям. В обзоре представлены особенности NK-клеток, полученных из периферической крови взрослого человека, пуповинной крови, эмбриональных стволовых клеток человека, индуцированных плюрипотентных стволовых клеток и линии клеток NK-92. Обсуждаются их характеристики в контексте применения для CAR-технологий.

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Irradiated Mononuclear Cells Express Significant In Vitro Cytotoxic Activity: Promise for In Vivo Clinical Efficacy of Irradiated Mismatched Donor Lymphocytes Infusion

Abstract: The efficacy of irradiated haploidentical lymphocytes should be further tested in a larger number of patients.

Cited by 7 publications

References 15 publications

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Donor lymphocyte infusions in AML and MDS: Enhancing the graft-versus-leukemia effect

Irradiation of peripheral blood mononuclear cells with 7.5 Gy X-rays prior to donor lymphocyte infusion inhibits proliferation while preserving cytotoxicity, and improves the effectiveness of HSCT in patients with hematological malignancies

Sources of NK Cells for CAR-Technologies

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