Fusions of Human Ovarian Carcinoma Cells with Autologous or Allogeneic Dendritic Cells Induce Antitumor Immunity

Gong, Jianlin; Nikrui, Najmosama; Chen, Dongshu; Koido, Shigeo; Wu, Zhiyou; Tanaka, Yasuhiro; Cannistra, Stephen A.; Avigan, David; Küfe, Donald

doi:10.4049/jimmunol.165.3.1705

Cited by 200 publications

(128 citation statements)

References 48 publications

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“…Allogeneic DCs have been proposed as an alternative approach for cancer immunotherapy with an argument that the alloagression offers a generic tool to promote an effective T cell response to self MHC-restricted tumor peptides (51). Although recent clinical trials failed to demonstrate immunogenicity of allogeneic DCs loaded with tumor lysates (52), several investigations have shown the Ag presentation and induction of a potent tumor-specific immune response by allogeneic DCs fused with syngeneic or autologous cancer cells (53)(54)(55)(56)(57). Thus, generation of allogeneic hES cell-derived DC/autologous cancer cell hybrids could be seen as a feasible approach to the development of hES cell-based vaccines.…”

Section: Discussionmentioning

confidence: 99%

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

Slukvin

Vodyanik

Thomson

et al. 2006

The Journal of Immunology

112

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We have established a system for directed differentiation of human embryonic stem (hES) cells into myeloid dendritic cells (DCs). As a first step, we induced hemopoietic differentiation by coculture of hES cells with OP9 stromal cells, and then, expanded myeloid cells with GM-CSF using a feeder-free culture system. Myeloid cells had a CD4+CD11b+CD11c+CD16+CD123lowHLA-DR− phenotype, expressed myeloperoxidase, and included a population of M-CSFR+ monocyte-lineage committed cells. Further culture of myeloid cells in serum-free medium with GM-CSF and IL-4 generated cells that had typical dendritic morphology; expressed high levels of MHC class I and II molecules, CD1a, CD11c, CD80, CD86, DC-SIGN, and CD40; and were capable of Ag processing, triggering naive T cells in MLR, and presenting Ags to specific T cell clones through the MHC class I pathway. Incubation of DCs with A23187 calcium ionophore for 48 h induced an expression of mature DC markers CD83 and fascin. The combination of GM-CSF with IL-4 provided the best conditions for DC differentiation. DCs obtained with GM-CSF and TNF-α coexpressed a high level of CD14, and had low stimulatory capacity in MLR. These data clearly demonstrate that hES cells can be used as a novel and unique source of hemopoietic and DC precursors as well as DCs at different stages of maturation to address essential questions of DC development and biology. In addition, because ES cells can be expanded without limit, they can be seen as a potential scalable source of cells for DC vaccines or DC-mediated induction of immune tolerance.

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Section: Discussionmentioning

confidence: 99%

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

Slukvin

Vodyanik

Thomson

et al. 2006

The Journal of Immunology

112

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“…In this approach, TAAs, including both known and unidentified Ags are delivered to DCs, processed, and presented through both MHC class I and II pathways in the context of costimulatory molecules (6). We have previously reported that immature (Imm) DCs (Imm-DCs) fused with autologous tumor cells can induce Ag-specific polyclonal CTLs in vitro (7)(8)(9)(10)(11). Although immunization with DC/tumor cell FCs in patients with cancer has been associated with immunological responses in phase I clinical trials, early clinical trials have shown only limited success (12)(13)(14)(15)(16)(17).…”

Section: Synergistic Induction Of Antigen-specific Ctl By Fusions Of mentioning

confidence: 99%

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- γ at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+IFN-γ+CD8+ T cells and CD154+ IFN-γ+CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

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“…24 Briefly, PBMCs were suspended in medium and allowed to adhere to plastic dishes. Following incubation for two hours at 37°, the non-adherent cells were removed, and the adherent cells were cultured with GM-CSF (800 U/ml) and IL-4 (500 U/ml) for 6 days in RPMI-1640 (Mediatech, Herndon, VA) supplemented with 1% human sera.…”

Section: Cell Culture and DC Generationmentioning

confidence: 99%

Induction of human papillomavirus type 16‐specific immunologic responses in a normal and an human papillomavirus‐infected populations

Cheng

Lee²,

et al. 2005

Immunology

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Human papillomavirus (HPV) infection represents the most important risk factor for developing cervical cancer. Although there are over 20 oncogenic HPV genotypes, HPV16 is the most prevalent type in cervical cancer compared with other HPV genotypes regardless of geographical origin. SummaryHuman papillomavirus (HPV) infection, especially with the oncogenic genotypes, is the most important risk factor for developing cervical cancer. We focused on generating HPV16 E7-specific cytotoxic CD8 + T lymphocytes and evaluating HPV16 E7-specific immune responses in HPV16-infected and uninfected populations. Peripheral blood mononuclear cells (PBMCs) were first collected from an uninfected group with an human lymphocyte antigen (HLA) A2 haplotype (four volunteers). Mature monocyte-derived dendritic cells (DCs) were generated from the PBMCs and pulsed with one of two HLA-A2-restricted E7 peptides, aa 11-20 [YMLDLQPETT] and aa 86-93 [TLGIVCPI], as antigen presenting cells. The autologous naïve or cultured PBMCs were then cultured with peptide-pulsed DCs to detect the HPV16 E7-specific immune responses by a variety of techniques such as enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) assay and cytotoxic T lymphocyte assay. Interferon-c (IFN-c) from E7-specific cytotoxic CD8 + T lymphocytes stimulated with the respective peptide was detected by ELISA. Using ELISPOT analysis, a marked increase in the number of IFN-c-secreting CD8 + E7-specific lymphocytes was observed following peptide stimulation. Cultured CD8 + T lymphocytes were highly cytotoxic against the CaSki cells. PBMCs were then colleted from an HPV16-infected population of the HLA-A2 haplotype, including four persons of HPV16 infection only, four with cervical intraepithelial neoplasia (CIN) lesions, and four cervical cancer patients. We then compared the immunologic responses to E7 between HPV16-infected and uninfected populations by ELISA and ELISPOT assay. The E7-specific immunologic responses of the HPV16-infected populations were significantly higher than those of the uninfected population. In addition, persons with an HPV16 infection only or those with CIN lesions generated higher E7-specific immunologic responses than cervical cancer patients. Our results demonstrate methods for evaluating E7-sepcific immunologic responses and reflect the biological responses of HPV16-infected people during different periods of cervical disease.

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Fusions of Human Ovarian Carcinoma Cells with Autologous or Allogeneic Dendritic Cells Induce Antitumor Immunity

Cited by 200 publications

References 48 publications

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Induction of human papillomavirus type 16‐specific immunologic responses in a normal and an human papillomavirus‐infected populations

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