Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1785088546369961984 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10419531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT parkjeonga promiseandchallengesoftcellimmunotherapyforosteosarcoma AT cheungnaikongv promiseandchallengesoftcellimmunotherapyforosteosarcoma |