Immune approaches to treating osteosarcoma

Marina, Nyessa; Görlick, Richard

doi:10.4161/cbt.8.10.8602

Cited by 5 publications

(1 citation statement)

References 26 publications

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“…In the last few years, many investigators have focused on immunotherapy and its applicability to OS (Marina and Gorlick, 2009). IFN has been employed either alone or in combination with chemotherapy, and ILs (e.g.…”

Section: Introductionmentioning

confidence: 99%

Invariant NKT cells increase drug‐induced osteosarcoma cell death

Fallarini

Paoletti

Battaglini

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSEIn osteosarcoma (OS) patients, only a limited number of drugs are active and the regimens currently in use include a combination of at least two of these drugs: doxorubicin, cisplatin, methotrexate and ifosfamide. Today, 30-40% of patients still die of OS highlighting the urgent need for new treatments. Invariant NKT (iNKT) cells are a lymphocyte lineage with features of both T and NK cells, playing important roles in tumour suppression. Our aim was to test whether the cytoxicity induced by cisplatin, doxorubicin and methotrexate against OS cells can be enhanced by iNKT cell treatment. EXPERIMENTAL APPROACHiNKT cells were purified from human peripheral blood mononuclear cells by cell sorting (Va24Vb11 + cells) and used as effector cells against OS cells (U2-OS, HOS, MG-63). Cell death (calcein-AM method), perforin/granzyme B and Fas/FasL expressions were determined by flow cytometry. CD1d expression was analysed at both the gene and protein level. KEY RESULTSiNKT cells were cytotoxic against OS cells through a CD1d-dependent mechanism. This activity was specific for tumour cells, because human CD1d + mesenchymal stem cells and CD1d -osteoblasts were not affected. iNKT cell treatment enhanced drug-induced OS cell death in a concentration-dependent manner and this effect was reduced in CD1d-silenced OS cells. CONCLUSION AND IMPLICATIONSiNKT cells kill malignant, but not non-malignant, cells. iNKT cell treatment enhances the cytotoxicity of anti-neoplastic drugs against OS cells in a CD1d-dependent manner. The present data encourage further studies on the use of iNKT cells in OS therapy.

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Section: Introductionmentioning

confidence: 99%

Invariant NKT cells increase drug‐induced osteosarcoma cell death

Fallarini

Paoletti

Battaglini

et al. 2012

British J Pharmacology

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Osteoimmunopathology

Chiappelli

2011

Osteoimmunopathology

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Potential of human γδ T cells for immunotherapy of osteosarcoma

2012

Mol Biol Rep

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Recurrent or metastatic osteosarcomas remain a challenging malignancy to treat. Therefore, development and testing of novel therapeutic strategies to target these patients are needed. Adoptive cellular therapy strategies are being evaluated intensively as a novel therapeutic strategy for cancer. Unlike αβ T cells requiring antigen processing and MHC-restricted peptide displayed by antigen-presenting cells, γδ T cells exhibit the potent MHC-unrestricted lytic activity against various tumors in vitro and in vivo. The recent considerable success of γδ T cell-based immunotherapy in lung metastasis of renal cell carcinoma warrants further efforts to apply this treatment to other cancers including osteosarcoma, especially recurrent and metastatic osteosarcomas. In this review, we summarize the available evidence on γδ T cell-based immunotherapy for osteosarcoma that has been achieved to date. More importantly, we discuss potential strategies of the combination of expanded γδ T cells and bisphosphonates, and modification and expansion of αβ TCR modified γδ T cells for improving its efficacy for the treatment of osteosarcoma.

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Immune approaches to treating osteosarcoma

Cited by 5 publications

References 26 publications

Invariant NKT cells increase drug‐induced osteosarcoma cell death

Invariant NKT cells increase drug‐induced osteosarcoma cell death

Osteoimmunopathology

Potential of human γδ T cells for immunotherapy of osteosarcoma

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