Article ; Online: [No title information]
2018 Volume 105 Suppl 2, Page(s) S178–S187
Abstract: Development of car t-cells in solid tumors: CHALLENGES AND PERSPECTIVES: While Chimeric Antigen Receptor (CAR) T-cells have shown outstanding results in some hematologic malignancies, studies in solid tumors are less encouraging with poor response rates. ...
Title translation | Développement des CAR-T dans les tumeurs solides. |
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Abstract | Development of car t-cells in solid tumors: CHALLENGES AND PERSPECTIVES: While Chimeric Antigen Receptor (CAR) T-cells have shown outstanding results in some hematologic malignancies, studies in solid tumors are less encouraging with poor response rates. Several factors can account for this lack of efficiency in solid tumors: heterogeneous expression or absence of specific target antigen (and so higher risk of toxicity), immunosuppressive microenvironment, homing and tumoral trafficking issues or lack of CAR T-cell persistence. Different approaches can be considered to overcome these resistance mechanisms: bispecific CARs, use of logic gates, combination with immune checkpoint inhibitors, engineered CAR T-cells resistant to immunosuppressive molecules, addition of chemokines or enzymes, combination with oncolytic virus, intra-tumoral administration, selection of memory T cell subpopulations and development of armored CAR T-cells secreting cytokines such as IL-12, -15 or -18. Last generation optimized CAR T-cell design should thus improve therapeutic efficiency. CAR-T cells may represent in a near future a therapeutic breakthrough also in solid tumors, especially in cold tumors and/or tumors lacking MHC class I expression. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene. |
MeSH term(s) | Antibody Specificity/immunology ; Clinical Trials as Topic ; Humans ; Immunotherapy, Adoptive/methods ; Interleukin-12/metabolism ; Interleukin-15/metabolism ; Interleukin-18/metabolism ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Chimeric Antigen/immunology ; Receptors, Lymphocyte Homing/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/immunology ; Treatment Outcome ; Tumor Microenvironment/immunology |
Chemical Substances | Interleukin-15 ; Interleukin-18 ; Receptors, Chimeric Antigen ; Receptors, Lymphocyte Homing ; Interleukin-12 (187348-17-0) |
Language | French |
Publishing date | 2018-10-26 |
Publishing country | France |
Document type | Journal Article ; Review |
ZDB-ID | 213270-9 |
ISSN | 1769-6917 ; 0007-4551 |
ISSN (online) | 1769-6917 |
ISSN | 0007-4551 |
DOI | 10.1016/S0007-4551(19)30048-7 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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