Establishment of stable cell lines for personalized melanoma cell vaccine

Selvan, Senthamil R.; Carbonell, Denysha; Fowler, Abner; Beatty, Andrea; Ravindranath, Mepur H.; Dillman, Robert O.

doi:10.1097/cmr.0b013e3283390696

Cited by 26 publications

(24 citation statements)

References 34 publications

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“…Autologous melanoma cell lines were generated separately from TILs either from tumor fragments or from a combination of cells recovered from suspension in transport medium or after mincing, as previously described (16,18).…”

Section: Generation Of Tils and Melanoma Cell Linesmentioning

confidence: 99%

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

et al. 2015

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Section: Generation Of Tils and Melanoma Cell Linesmentioning

confidence: 99%

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

et al. 2015

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“…Cell line authentication was carried out by an STR identifier kit (Applied Biosystems) and both cell lines used in the study showed at least a 90% match to the STR profiles of ESTDAB (Supplementary Table S1). The early-passage GEWA and KADA melanoma cell lines were established from patients at the oncology clinic at Karolinska University Hospital (ethical permit: #2011/143-32/1) based on the published protocol (25). Mycoplasma-free (MycoAlert kit) GEWA and KADA cell lines were in their 7 th and 6 th passage when used for tumormonocyte coculture, respectively.…”

Section: Tumor Coculture and Mdsc Isolationmentioning

confidence: 99%

Melanoma-Educated CD14+ Cells Acquire a Myeloid-Derived Suppressor Cell Phenotype through COX-2–Dependent Mechanisms

et al. 2013

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Tumors can suppress the host immune system by employing a variety of cellular immune modulators, such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). In the peripheral blood of patients with advanced stage melanoma, there is an accumulation of CD14 þ HLA-DR lo/À MDSC that suppress autologous T cells ex vivo in a STAT-3-dependent manner. However, a precise mechanistic basis underlying this effect is unclear, particularly with regard to whether the MDSC induction mechanism relies on cell-cell contact of melanoma cells with CD14 þ cells. Here, we show that early-passage human melanoma cells induce phenotypic changes in CD14 þ monocytes, leading them to resemble MDSCs characterized in patients with advanced stage melanoma. These MDSC-like cells potently suppress autologous T-cell proliferation and IFN-g production. Notably, induction of myeloid-suppressive functions requires contact or close proximity between monocytes and tumor cells. Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14 þ cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE 2 ), STAT-3, and superoxide. Indeed, PGE 2 was sufficient to confer to monocytes the ability to suppress proliferation and IFN-g production by autologous T cells ex vivo. In summary, our results reveal how immune suppression by MDSC can be initiated in the tumor microenvironment of human melanoma. Cancer Res; 73(13); 3877-87. Ó2013 AACR.

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“…25 Generation of a DC vaccine employing purified autologous tumor cells as the antigen source has been shown to be feasible and perhaps preferable by virtue of containing a patient-specific repertoire of tumor-associated antigens. 18,26 The difficulty and expense of generating purified autologous cell lines may be outweighed by the benefits of having the full complement of tumor-associated antigens in the patient-specific product. Some clinical trials are using unpurified autologous bulk tumors with some success; however, it is not known whether contaminating fibroblasts and/or necrotic tissue affect the immunotherapeutic product.…”

Section: Discussionmentioning

confidence: 99%

“…Pure tumor cells generated and characterized as previously reported [16][17][18] were expanded to 200 million cells and then incubated with 1000 IU/mL of IFN-c (InterMune) for 72 hours in 15% FBS/ECS in RPMI (complete medium), irradiated with 100 Gy from a cesium source, and cryopreserved as previously described. 19 The IFN-c-treated and irradiated tumor cells were recovered from cryopreservation, washed 3 · with PBS, and then added to the in vitro cultivated DCs and incubated for *24 hours.…”

Section: Autologous Tumor Cell Line Generationmentioning

confidence: 99%

Characterization of Interferon-γ–Treated Melanoma Tumor Cells for Use in Dendritic Cell-Based Immunotherapy

Cornforth

Fowler

Carbonell

et al. 2011

Cancer Biotherapy and Radiopharmaceuticals

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Efficient delivery of tumor-associated antigens to professional antigen-presenting cells is important for inducing a response in patients receiving cancer immunotherapy. Interferon-gamma (IFN-γ) is used by the immune system to combat viral and fungal infections by restricting cell proliferation and, in some cases, inducing apoptosis. Using IFN-γ to activate target tumor cells prior to antigen loading of dendritic cells (DCs) may enhance the beneficial qualities of whole-cell tumor vaccines. The incubation of melanoma cell cultures with IFN-γ resulted in an increase in the expression of major histocompatibility complex molecules and ICAM-1 but generally decreased the expression of melanoma-associated tumor antigens. Additionally, important immune-stimulating molecules (heat-shock proteins, high-mobility group box-1 protein, and calreticulin) were also present but differentially regulated by IFN-γ. Loading of DCs with IFN-γ-treated tumor cells resulted in a small but significant increase in the expression of CD83-positive DCs, indicating the initiation of DC maturation (p=0.019). IFN-γ treatment of melanoma cell lines prior to antigen loading of DCs may aid in antigen processing and presentation.

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Establishment of stable cell lines for personalized melanoma cell vaccine

Cited by 26 publications

References 34 publications

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

Melanoma-Educated CD14+ Cells Acquire a Myeloid-Derived Suppressor Cell Phenotype through COX-2–Dependent Mechanisms

Characterization of Interferon-γ–Treated Melanoma Tumor Cells for Use in Dendritic Cell-Based Immunotherapy

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