Immunotherapy of sarcomas with modified T cells

Mahalingam, Preethika; Julve, Maximilian; Huang, Paul H.; Furness, Andrew; Pollack, Seth M.; Jones, Robin L.

doi:10.1097/cco.0000000000000843

Cited by 5 publications

(2 citation statements)

References 98 publications

(140 reference statements)

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“…Studies have found that HLA-A*02 is more common in Caucasian populations compared to African-American and Asian populations ( 63 ). Other barriers for ACT include the multi-week time needed for the production of genetically engineered T-cells, the pre-treatment lymphodepletion regimen which often requires hospitalization, and the high cost of therapy ( 64 , 65 ). While many of these issues may be overcome through improvement in manufacturing techniques and health systems changes, some may be incontrovertible.…”

Section: Syn Antigen Expression and Adopted Cell Transfermentioning

confidence: 99%

Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma

et al. 2023

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Synovial sarcoma is a soft tissue sarcoma accounting for approximately 1,000 cases per year in the United States. Currently, standard treatment of advanced and metastatic synovial sarcoma is anthracycline-based chemotherapy. While advanced synovial sarcoma is more responsive to chemotherapy compared to other soft tissue sarcomas, survival rates are poor, with a median survival time of less than 18 months. Enhanced understanding of tumor antigen expression and molecular mechanisms behind synovial sarcoma provide potential targets for treatment. Adoptive Cell Transfer using engineered T-cell receptors is in clinical trials for treatment of synovial sarcoma, specifically targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1), preferentially expressed antigen in melanoma (PRAME), and melanoma antigen-A4 (MAGE-A4). In this review, we explore the opportunities and challenges of these treatments. We also describe artificial adjuvant vector cells (aAVCs) and BRD9 inhibitors, two additional potential targets for treatment of advanced synovial sarcoma. This review demonstrates the progress that has been made in treatment of synovial sarcoma and highlights the future study and qualification needed to implement these technologies as standard of care.

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Section: Syn Antigen Expression and Adopted Cell Transfermentioning

confidence: 99%

Emerging targeted and cellular therapies in the treatment of advanced and metastatic synovial sarcoma

et al. 2023

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“…GD-2-specific CAR-T cells, as well as CAR-T cells specific to other sarcoma markers, CD133, HER2, Muc1 and CD117 are being tested in clinical trials (NCT03356782, NCT03356782, NCT04433221). Therapeutic approaches in sarcoma based on modified T cells have recently been reviewed [178]. However, the HLA restriction of T-cell-based therapies to prevent GvHD, limits the streamlining of the manufacturing processes and limit the therapy mainly to autologous sources.…”

Section: Nk Cell Engineeringmentioning

confidence: 99%

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas

Bareke,

Ibáñez-Navarro,

Guerra-García

et al. 2023

IJMS

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Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.

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