Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
Alain E. Andrea,Andrada Chiron,Sarah Mallah,Stéphanie Bessoles,Guillaume Sarrabayrouse,Salima Hacein-Bey-Abina +5 more
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TLDR
An overview of the major mechanisms used by tumor cells to evade immune defenses is provided and the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors are critically exposed.Abstract:
During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors.read more
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Recent Advances and Challenges in Cancer Immunotherapy
TL;DR: The current landscape of immuno-oncology research is discussed, with a focus on elements that influence immunotherapeutic outcomes, and the role of the immunosuppressive cells within the tumor microenvironment in regulating antitumor immunity is highlighted.
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Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors
Katerina Kalkusova,Sindija Šmite,Elea Darras,Pavla Taborska,Dmitry Stakheev,Luca Vannucci,Jirina Bartunkova,Daniel Smrz +7 more
TL;DR: In this paper , the authors discuss how the immune cells can be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system and also discuss how this modulation could be used to improve the immunotherapy performance.
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CAR T-Cell therapy for the management of mantle cell lymphoma
TL;DR: In this paper , a brief synopsis of the development of CAR T-cell therapy for MCL is presented, and the FDA has approved brexucabtagene autoleucel (Tecartus, KTE-X19) to be used in patients with MCL who have not responded to previous treatments or have relapsed.
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Regulation of autophagy fires up the cold tumor microenvironment to improve cancer immunotherapy
TL;DR: Targeted autophagy ignites immunosuppressive TME by influencing antigen release, antigen presentation, antigen recognition, and immune cell trafficking, thereby enhancing the effectiveness of cancer immunotherapy and overcoming resistance to immunotherapy.
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Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
TL;DR: In this paper , the authors summarized the efficacy, safety, and challenges of CAR T-cell therapy in the clinical management of solid tumors, and discussed the potential strategies currently applied to improve the efficacy and safety of CAR-T-cells in solid tumors.
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