| Author | Donnadieu, Emmanuel | |
| Author | Dupré, Loïc | |
| Author | Pinho, Lia Gonçalves | |
| Author | Almeida, Vinicius Cotta de | |
| Access date | 2021-01-10T14:54:06Z | |
| Available date | 2021-01-10T14:54:06Z | |
| Document date | 2020 | |
| Citation | DONNADIEU, Emmanuel et al. Surmounting the obstacles that impede effective CAR T cell trafficking to solid tumors. Journal of Leukocyte Biology, v. 108, p. 1067-1079, 2020. | pt_BR |
| ISSN | 1938-3673 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45548 | |
| Language | eng | pt_BR |
| Publisher | Wiley Online Library | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Imunoterapia contra o câncer | pt_BR |
| Subject in Portuguese | Tráfico de células T | pt_BR |
| Subject in Portuguese | Engenharia de receptor de antígeno quimérico | pt_BR |
| Subject in Portuguese | Motilidade | pt_BR |
| Subject in Portuguese | Matriz extracelular | pt_BR |
| Subject in Portuguese | Microambiente tumoral | pt_BR |
| Title | Surmounting the obstacles that impede effective CAR Tcell trafficking to solid tumors | pt_BR |
| Type | Article | |
| DOI | 10.1002/JLB.1MR0520-746R | |
| Abstract | Innovative immunotherapies based on immune checkpoint targeting antibodies and engineered
T cells are transforming the way we approach cancer treatment. However, although these T cell
centered strategies result in marked and durable responses in patients across many different
tumor types, they provide therapeutic efficacy only in a proportion of patients. A major challenge
of immuno-oncology is thereby to identify mechanisms responsible for resistance to cancer
immunotherapy in order to overcome them via adapted strategies thatwill ultimately improve
intrinsic efficacy and response rates. Here, we focus on the barriers that restrain the trafficking
of chimeric antigen receptor (CAR)-expressing T cells to solid tumors. Upon infusion, CAR T cells
need to home into malignant sites, navigate within complex tumor environments, form productive
interactions with cancer cells, deliver their cytotoxic activities, and finally persist.We review
the accumulating evidence that the microenvironment of solid tumors contains multiple obstacles
that hinder CAR T cells in the dynamic steps underlying their trafficking.We focus on how these
hurdles may in part account for the failure of CAR T cell clinical trials in human carcinomas. Given
the engineered nature of CAR T cells and possibilities to modify the tumor environment, there
are ample opportunities to augment CAR T cell ability to efficiently find and combat tumors.We
present some of these strategies, which represent a dynamic field of research with high potential
for clinical applicability. | pt_BR |
| Affilliation | Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104. Paris, France. | pt_BR |
| Affilliation | INSERM, UMR1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France / CNRS, UMR5282. Toulouse, France / Université Toulouse III Paul-Sabatier, Toulouse, France. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Imunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Imunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Cancer immunotherapy | pt_BR |
| Subject | T cell trafficking | pt_BR |
| Subject | Chimeric antigen receptor engineering | pt_BR |
| Subject | Motility | pt_BR |
| Subject | Extracellular matrix | pt_BR |
| Subject | Tumor microenvironment | pt_BR |
| xmlui.metadata.dc.subject.ods | 05 Igualdade de gênero | |
| xmlui.metadata.dc.subject.ods | 16 Paz, Justiça e Instituições Eficazes | |
