Adoptive Cell Therapy for Sarcoma

Mata, Melinda

doi:10.2217/imt.14.98

Cited by 11 publications

(9 citation statements)

References 152 publications

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“…An alternative approach to alteration of the tumor microenvironment is the introduction of autologous T-cells with enhanced activity against a specific tumor epitope. Instead of systemic modification of the immune system with a receptor antibody such as an anti-PD1, this approach allows direct introduction of a confirmed tumor antigen in an effort to activate the immune system against the neoplasm (64). Currently two main technologies of adoptive T cell immunotherapies are being utilized; in one method chimeric antibody receptor engineered T cell (CAR-T) which focuses on helping the immune cells recognize the tumor antigens and then directing them to locate and kill the target tumor cells.…”

Section: T-cell Targeted Approachmentioning

confidence: 99%

Turning ‘Cold’ tumors ‘Hot’: immunotherapies in sarcoma

Rytlewski¹,

Milhem²,

Monga³

2021

Ann Transl Med

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Immunotherapies have an established role in the management of several advanced malignancies.Their responses are largely dependent on the presence of PD-L1, microsatellite instability (MSI), and high tumor mutation burden. Sarcomas are heterogenous tumors which comprise over 100 subtypes.They are broadly considered immunologically inert or "cold". Immunotherapy as monotherapy has shown interesting responses in a certain handful of subtypes, such as undifferentiated pleomorphic sarcoma, dedifferentiated and pleomorphic liposarcoma, and alveolar soft part sarcoma. However, the mechanisms of action of immunotherapy agents in several sarcoma subtypes remains unknown. Several sarcoma types such as leiomyosarcoma have been shown to have an immunosuppressive microenvironment. Early clinical studies suggest the emergence of B cell infiltration in sarcoma tumor tissues as well as the role of PD-1 and PD-L1 as biomarkers of response. Immunotherapy combinations with conventional chemotherapies, radiation therapies, tyrosine kinase inhibitors and oncolytic viruses are showing promise in turning these "cold" tumors "hot". Several novel agents as well as repurposing therapies with the potential to enhance immunotherapy responses are undergoing pre-clinical and clinical studies in other tumor types. Herein we review current clinical studies which have explored the use of immunotherapeutic agents in the management of sarcomas and discuss the challenges and future directions.

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Section: T-cell Targeted Approachmentioning

confidence: 99%

Turning ‘Cold’ tumors ‘Hot’: immunotherapies in sarcoma

Rytlewski¹,

Milhem²,

Monga³

2021

Ann Transl Med

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“…It was demonstrated that a marked increase in IFN-γ, GM-CSF, TNF-α, IL-6, and IL-10 occurred shortly after the lymphocyte infusion ( 108 ). Incorporation of suicide genes or engineering of multi-specific CAR-T cells to limit their activation to tumor sites might allow control of adverse events ( 109 ). In summary, adoptive transfer of CAR-T cells appears to be an attractive therapeutic option for experimental osteosarcoma therapy, but further research will be required to develop comprehensive measures to avoid adverse side effects.…”

Section: Adoptive T Cell Transfer For Osteosarcomamentioning

confidence: 99%

T-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities

Wang

Ren

et al. 2016

Front. Immunol.

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Even though combining surgery with chemotherapy has significantly improved the prognosis of osteosarcoma patients, advanced, metastatic, or recurrent osteosarcomas are often non-responsive to chemotherapy, making development of novel efficient therapeutic methods an urgent need. Adoptive immunotherapy has the potential to be a useful non-surgical modality for treatment of osteosarcoma. Recently, alternative strategies, including immunotherapies using naturally occurring or genetically modified T cells, have been found to hold promise in the treatment of hematologic malignancies and solid tumors. In this review, we will discuss possible T-cell-based therapies against osteosarcoma with a special emphasis on combination strategies to improve the effectiveness of adoptive T cell transfer and, thus, to provide a rationale for the clinical development of immunotherapies.

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“…Cytokines mediate various activities of the cells involved in innate immunity. T and B Various subtypes of sarcomas express TAAs that allow the development of cellular immunotherapies [20]. In particular, some sarcomas have specific chromosomal translocations that may serve as unique targets for immunotherapy [21].…”

Section: Target Of Cellular Immunotherapymentioning

confidence: 99%

Current Status of Immunotherapy for Sarcomas

2017

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Although the development of anticancer drugs has improved the outcomes of bone and soft tissue sarcomas, the clinical outcome of patients with relapsed sarcomas remains unsatisfactory due to therapeutic toxicities and resistance to anticancer drugs. Therefore, novel therapeutic modalities are needed to improve the outcome of patients with bone and soft tissue sarcomas. Dendritic cells present tumor antigens and stimulate immune responses, and immune cells, such as cytotoxic T lymphocytes, kill tumor cells by recognizing tumor antigens. However, immune-suppressive conditions by immune regulator PD-1, CTLA-4 and regulatory T cells help tumor growth and progression. In this report, current immunotherapies including cellular immunotherapy and checkpoint inhibitors are introduced, and the advantages and disadvantages of the treatments are discussed.

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Adoptive Cell Therapy for Sarcoma

Cited by 11 publications

References 152 publications

Turning ‘Cold’ tumors ‘Hot’: immunotherapies in sarcoma

Turning ‘Cold’ tumors ‘Hot’: immunotherapies in sarcoma

T-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities

Current Status of Immunotherapy for Sarcomas

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