Importance of T, NK, CAR T and CAR NK Cell Metabolic Fitness for Effective Anti-Cancer Therapy: A Continuous Learning Process Allowing the Optimization of T, NK and CAR-Based Anti-Cancer Therapies.
Simple Summary: Cancer treatments are evolving at a very rapid pace. Some of the most novel anti-cancer medicines under development rely on the modification of immune cells in order to transform them into potent tumor-killing cells. However, the tumor microenvironment (TME) is competing for nutrient...
| Publicado en: | Cancers Vol. 14; no. 1; pp. 183 - 184 |
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| Autores principales: | , , |
| Formato: | pictorial review tables/charts Journal Article |
| Publicado: |
MDPI
Jan2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=154587679&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 154587679 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jan2022 vid: 14 iid: 1 pid: 97109 pub: MDPI artinfo: ui: 154587679 154587679 154587679 10.3390/cancers14010183 154587679 ppf: 183 ppct: 1 formats: tig: atl: Importance of T, NK, CAR T and CAR NK Cell Metabolic Fitness for Effective Anti-Cancer Therapy: A Continuous Learning Process Allowing the Optimization of T, NK and CAR-Based Anti-Cancer Therapies. aug: au: Krug, Adrien Martinez-Turtos, Adriana Verhoeyen, Els affil: Université Côte d'Azur, INSERM, C3M, 06204 Nice, France sug: subj: Antineoplastic Agents Therapeutic Use Lifelong Learning Killer Cells, Natural Metabolism Receptors, Cell Surface Metabolism Immunotherapy Cell Physiology Metabolic Networks and Pathways Nutrients Glucose Metabolism Physical Fitness Glycolysis ab: Simple Summary: Cancer treatments are evolving at a very rapid pace. Some of the most novel anti-cancer medicines under development rely on the modification of immune cells in order to transform them into potent tumor-killing cells. However, the tumor microenvironment (TME) is competing for nutrients with these harnessed immune cells and therefore paralyzes their metabolic effective and active anti-cancer activities. Here we describe strategies to overcome these hurdles imposed on immune cell activity, which lead to therapeutic approaches to enhance metabolic fitness of the patient's immune system with the objective to improve their anti-cancer capacity. Chimeric antigen receptor (CAR) T and CAR NK cell therapies opened new avenues for cancer treatment. Although original successes of CAR T and CAR NK cells for the treatment of hematological malignancies were extraordinary, several obstacles have since been revealed, in particular their use for the treatment of solid cancers. The tumor microenvironment (TME) is competing for nutrients with T and NK cells and their CAR-expressing counterparts, paralyzing their metabolic effective and active states. Consequently, this can lead to alterations in their anti-tumoral capacity and persistence in vivo. High glucose uptake and the depletion of key amino acids by the TME can deprive T and NK cells of energy and building blocks, which turns them into a state of anergy, where they are unable to exert cytotoxic activity against cancer cells. This is especially true in the context of an immune-suppressive TME. In order to re-invigorate the T, NK, CAR T and CAR NK cell-mediated antitumor response, the field is now attempting to understand how metabolic pathways might change T and NK responses and functions, as well as those from their CAR-expressing partners. This revealed ways to metabolically rewire these cells by using metabolic enhancers or optimizing pre-infusion in vitro cultures of these cells. Importantly, next-generation CAR T and CAR NK products might include in the future the necessary metabolic requirements by improving their design, manufacturing process and other parameters. This will allow the overcoming of current limitations due to their interaction with the suppressive TME. In a clinical setting, this might improve their anti-cancer effector activity in synergy with immunotherapies. In this review, we discuss how the tumor cells and TME interfere with T and NK cell metabolic requirements. This may potentially lead to therapeutic approaches that enhance the metabolic fitness of CAR T and CAR NK cells, with the objective to improve their anti-cancer capacity. pubtype: Academic Journal doctype: pictorial review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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