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Current landscape of CAR-therapy for osteosarcoma and rhabdomyosarcoma
Maria Stavrou1,2, Tatiana Nicolaou1, Maria Georgalli1
1Department of Translational Research and Precision Medicine, Cyprus Cancer Research Institute (CCRI), Nicosia, Cyprus.
Abstract:
Osteosarcoma (OS) and rhabdomyosarcoma (RMS) are the most prevalent pediatric sarcoma subtypes of the bones and soft tissues respectively. The lack in targeted treatment approaches alongside the generally dismal prognosis in the metastatic setting render the discovery of novel therapeutic modalities for these diseases a pressing need. Chimeric antigen receptor (CAR)-therapy has emerged as an innovative strategy for cancer management with marked success in the treatment of hematological malignancies. The specific approach employs genetic engineering to redirect the specificity of immune cells, primarily T cells, through the exogenous expression of fully synthetic receptors, eventually arming them with the capacity to recognize tumor associated antigens (TAA). CAR-based treatment for OS and RMS has been under investigation in pre-clinical studies over the past few years, while the first promising results from a clinical trial have recently been published. However, the so far limited efficacy of CAR-therapy in solid tumors due to various constraining factors, such as poor CAR-T cell trafficking to the tumor, minimal tumor infiltration and reduced in vivo persistence, still needs to be properly addressed. In this mini review we focus on the most recent CAR-therapy strategies explored in OS and RMS while we briefly review the evolution of CARs through the years and highlight existing challenges in the CAR field.
Insights
Chimeric antigen receptor (CAR)-therapy shows promise for pediatric bone and soft tissue sarcomas (osteosarcoma and rhabdomyosarcoma). Addressing challenges like tumor infiltration is key to improving CAR-T cell therapy efficacy in solid tumors.
Area of Science:
- Oncology
- Immunotherapy
- Pediatric Cancer Research
Background:
- Osteosarcoma (OS) and rhabdomyosarcoma (RMS) are common pediatric sarcomas with poor outcomes, especially in metastatic stages.
- Current treatments lack targeted approaches, necessitating novel therapeutic strategies.
- Chimeric antigen receptor (CAR)-therapy, successful in hematologic cancers, offers a new avenue for solid tumors.
Purpose of the Study:
- To review recent advancements in CAR-therapy for pediatric OS and RMS.
- To highlight the evolution of CAR constructs and their application in solid tumors.
- To discuss existing challenges and future directions for CAR-therapy in these pediatric sarcomas.
Main Methods:
- Review of pre-clinical studies and early clinical trial data on CAR-therapy for OS and RMS.
- Analysis of CAR engineering strategies and their impact on T cell function.
- Examination of factors limiting CAR-T cell efficacy in solid tumors.
Main Results:
- CAR-based strategies are under investigation for OS and RMS, with initial promising clinical results.
- Pre-clinical research has explored various CAR designs to enhance tumor recognition and immune cell activity.
- Challenges such as poor CAR-T cell trafficking, tumor infiltration, and persistence remain significant hurdles.
Conclusions:
- CAR-therapy represents an innovative approach for pediatric sarcomas, but its efficacy in solid tumors requires further optimization.
- Overcoming physical and immunological barriers within the tumor microenvironment is crucial for successful CAR-T cell therapy.
- Continued research into novel CAR designs and combination strategies is essential to improve outcomes for patients with OS and RMS.
