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Promise and Challenges of T Cell Immunotherapy for Osteosarcoma

The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agent...

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Autores principales: Park, Jeong A, Cheung, Nai-Kong V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419531/
https://www.ncbi.nlm.nih.gov/pubmed/37569894
http://dx.doi.org/10.3390/ijms241512520
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author Park, Jeong A
Cheung, Nai-Kong V.
author_facet Park, Jeong A
Cheung, Nai-Kong V.
author_sort Park, Jeong A
collection PubMed
description The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. However, osteosarcoma is an inherently heterogeneous tumor, both at the intra- and inter-tumor level, with no identical driver mutations. It has a pro-tumoral microenvironment, where bone cells, stromal cells, neovasculature, suppressive immune cells, and a mineralized extracellular matrix (ECM) combine to derail T cell infiltration and its anti-tumor function. To realize the potential of T cell immunotherapy in osteosarcoma, an integrated approach targeting this complex ecosystem needs smart planning and execution. Herein, we review the current status of T cell immunotherapies for osteosarcoma, summarize the challenges encountered, and explore combination strategies to overcome these hurdles, with the ultimate goal of curing osteosarcoma with less acute and long-term side effects.
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spelling pubmed-104195312023-08-12 Promise and Challenges of T Cell Immunotherapy for Osteosarcoma Park, Jeong A Cheung, Nai-Kong V. Int J Mol Sci Review The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. However, osteosarcoma is an inherently heterogeneous tumor, both at the intra- and inter-tumor level, with no identical driver mutations. It has a pro-tumoral microenvironment, where bone cells, stromal cells, neovasculature, suppressive immune cells, and a mineralized extracellular matrix (ECM) combine to derail T cell infiltration and its anti-tumor function. To realize the potential of T cell immunotherapy in osteosarcoma, an integrated approach targeting this complex ecosystem needs smart planning and execution. Herein, we review the current status of T cell immunotherapies for osteosarcoma, summarize the challenges encountered, and explore combination strategies to overcome these hurdles, with the ultimate goal of curing osteosarcoma with less acute and long-term side effects. MDPI 2023-08-07 /pmc/articles/PMC10419531/ /pubmed/37569894 http://dx.doi.org/10.3390/ijms241512520 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Park, Jeong A
Cheung, Nai-Kong V.
Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title_full Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title_fullStr Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title_full_unstemmed Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title_short Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
title_sort promise and challenges of t cell immunotherapy for osteosarcoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10419531/
https://www.ncbi.nlm.nih.gov/pubmed/37569894
http://dx.doi.org/10.3390/ijms241512520
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