Adoptive Cell Therapy in Treating Pediatric Solid Tumors

Tesfaye, Mekdem; Savoldo, Barbara

doi:10.1007/s11912-018-0715-9

Cited by 13 publications

(10 citation statements)

References 99 publications

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“…Even though successes have been achieved in several hematological malignancies [77][78][79][80], translation of these successes to solid tumors is difficult. Target expression heterogeneity, localization to the tumor site, and overcoming the immunosuppressive, nutrient-, and stimuli-deprived TME are thought to be the main challenges in effective adoptive cell therapy in solid tumors [81].…”

Section: Adoptive Cell Therapymentioning

confidence: 99%

Monitoring Immune Responses in Neuroblastoma Patients during Therapy

Szanto

Cornel

Vijver

et al. 2020

Cancers

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Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood. Despite intense treatment, children with this high-risk disease have a poor prognosis. Immunotherapy showed a significant improvement in event-free survival in high-risk NBL patients receiving chimeric anti-GD2 in combination with cytokines and isotretinoin after myeloablative consolidation therapy. However, response to immunotherapy varies widely, and often therapy is stopped due to severe toxicities. Objective markers that help to predict which patients will respond or develop toxicity to a certain treatment are lacking. Immunotherapy guided via immune monitoring protocols will help to identify responders as early as possible, to decipher the immune response at play, and to adjust or develop new treatment strategies. In this review, we summarize recent studies investigating frequency and phenotype of immune cells in NBL patients prior and during current treatment protocols and highlight how these findings are related to clinical outcome. In addition, we discuss potential targets to improve immunogenicity and strategies that may help to improve therapy efficacy. We conclude that immune monitoring during therapy of NBL patients is essential to identify predictive biomarkers to guide patients towards effective treatment, with limited toxicities and optimal quality of life.

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Section: Adoptive Cell Therapymentioning

confidence: 99%

Monitoring Immune Responses in Neuroblastoma Patients during Therapy

Szanto

Cornel

Vijver

et al. 2020

Cancers

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“…5. Глазное дно: аглазное дно OD К1, опухолевые очаги; бнормальное глазное дно OS К1 таких как нейробластома, гепатоцеллюлярная карцинома, саркомы мягких тканей и глиомы головного мозга [18]. Применение человеческих ЦТЛ при макроскопической РБ может быть оправданным с целью создания внутриглазного иммунитета, так как известно, что глаз обладает весьма скудной лимфатической системой.…”

Section: Discussionunclassified

Experimental Immunotherapy Model of Retinoblastoma

Ushakova

Долгополов

Соколова

et al. 2019

Rossijskij bioterapevtičeskij žurnal

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Introduction. The main reason for enucleation of the eye when attempting organ-preserving treatment are intraocular tumors that do not respond well to chemotherapy.Purpose. The aim of the study was to find new effective and safe organ-preserving methods of treatment of intraocular refractory and recurrent retinoblastoma (RB).Materials and methods. The study included female chinchilla rabbits. The cell line of human RB was intravitreally inserted into the right eye of each animal. The left eye was a control. After obtaining a stable intraocular growth of RB and prolongation of the growth of RB, human cytotoxic lymphocytes (CTL) were intravitreally injected into the affected and control eye K1 at a concentration of 1 × 106 in 0.1 ml suspension and K2 – 5 × 106 in 0.1 ml, respectively.Results. Histological examination of the removed right eyes in animals confirmed the presence of nodal growth of malignant small-cell tumor on the border of the vascular and retinal membranes (epicenter in the choroid) on the posterior wall of the eye. There was scant lymphoid infiltration, without signs of therapeutic pathomorphosis. In the removed animal»s left eyes there is a preservation of histological structures of the eyeball, without dystrophic changes in the cells of the retina and vascular membranes. In the area of limb unit microcap lymphohistiocytic infiltration (with no elements of the tumor). In the choroid single scattered lymphocytes.Conclusion. A short period of observation of the tumor did not allow conclusions about the effectiveness of CTL, but the concentrations of CTL used in the experiment did not lead to dystrophic changes in retinal cells and the choroid of the eye, which is an important factor in overcoming the toxicity of the proposed adoptive immunotherapy. At the next stage of the experiment, in our opinion, it is necessary to study in more detail the cytotoxic effect on healthy structures of the eye and the effectiveness of CTL in a larger number of affected rabbit eyes, using their different concentrations and multiplicity of administration.

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“…Adoptive cell therapy is one of the most promising immunotherapies that transfer the ex vivo expanded or engineered cells into the patients to improve and enhance immune functionality. However, in vivo experiments show that only a small number of the transferred cells reach the target site, thus limiting the therapeutic effects of the cell therapy (83). When the therapeutic cells are magnetized with magnetic NPs or microparticles, an external MF could guide the cells into the target site in vivo.…”

Section: Mf-related Immune Therapymentioning

confidence: 99%

Innate Immune Regulation Under Magnetic Fields With Possible Mechanisms and Therapeutic Applications

Lei

Pan

et al. 2020

Front. Immunol.

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With the wide applications of magnetic fields (MFs) in medicine, researchers from different disciplines have gained interest in understanding the effect of various types of MFs on living cells and organisms. In this paper, we mainly focus on the immunological and physical aspects of the immune responses and their mechanisms under different types of MFs. Immune cells were slightly affected by low-frequency alternating MFs but were strongly influenced by moderate-intensity MFs and high-gradient MFs (HGMFs). Larger immune cells, such as macrophages, were more sensitive to HGMFs, which biased the cell polarization into the anti-inflammatory M2 phenotype. Subject to the gradient forces of varying directions and strength, the elongated M2 macrophage also remodeled the cytoskeleton with actin polymerization and changed the membrane receptors and ion channel gating. These alterations were very similar to changes caused by the small GTPase RhoA interference in macrophage. Regulation of iron metabolism may also contribute to the MF effects in macrophages. High MFs were found to regulate the iron content in monocyte-/macrophage-derived osteoclasts by affecting the expression of iron-regulation genes. On the other hand, paramagnetic nanoparticles (NPs) combined with external MFs play an important role in T-cell immunity. Paramagnetic NP-coated Tcells can cluster their T-cell receptors (TCRs) by using an external MF, thus increasing the cell-cell contact and communication followed by enhanced tumor killing capacity. The external MF can also guide the adoptively transferred magnetic NP-coated T-cells to their target sites in vivo, thus dramatically increasing the efficiency of cell therapy. Additionally, iron oxide NPs for ferroptosis-based cancer therapy and other MF-related therapeutic applications with obstacles were also addressed. Furthermore, for a profound understanding of the effect of MFs on immune cells, multidisciplinary research involving both experimental research and theoretical modeling is essential.

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Adoptive Cell Therapy in Treating Pediatric Solid Tumors

Cited by 13 publications

References 99 publications

Monitoring Immune Responses in Neuroblastoma Patients during Therapy

Monitoring Immune Responses in Neuroblastoma Patients during Therapy

Experimental Immunotherapy Model of Retinoblastoma

Innate Immune Regulation Under Magnetic Fields With Possible Mechanisms and Therapeutic Applications

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