Antigen-specific active immunotherapy for ovarian cancer

Leffers, Ninke; Daemen, Toos; Helfrich, Wijnand; Boezen, H. Marike; Cohlen, Ben J; Melief, Cornelis J.M.; Nijman, Hans W.

doi:10.1002/14651858.cd007287.pub3

Cited by 22 publications

(12 citation statements)

References 96 publications

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“…In addition, immunotherapy was reported to effectively improve patients' autonomic anticancer immunity, strengthen their physique, reduce chemotherapy resistance, enhance the effect of chemotherapy on ovarian cancer and extend the valid period of survival (10). Antigen-specific active immunotherapy aims to induce tumor-antigen-specific antitumor immune responses, and has emerged as an alternative treatment for ovarian cancer (36). In the process of an immune response, tumor antigens are processed by APCs and presented to CTLs (14).…”

Section: Discussionmentioning

confidence: 99%

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer

Sui

et al. 2016

Oncology Letters

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Abstract. The present study aimed to establish a novel method for efficiently inducing cytotoxic T lymphocytes (CTLs) in vitro, in order to develop an immune-based therapy for suppressing and killing ovarian cancer cells with a high safety and efficacy. Peripheral blood mononuclear cells (PBMCs) were stimulated with CpG oligodeoxynucleotide (CpGODN) and ginsenoside Rg1, which were united as an immune adjuvant, and human epidermal growth factor receptor 2 (HER2/neu) antigen peptide, in order to establish a specific CTL culture system in vitro. Chromosome karyotype analysis, growth curve construction and flow cytometric analysis of immune phenotypes, including cluster of differentiation (CD)3, CD4 and CD8, were performed to characterize the stimulated PBMCs in vitro. Subsequently, SKOV3 ovarian cancer cells were treated with the specific CTL culture system in vitro, and MTT assays were performed to test the inhibitory and lethal effects of the CTLs on SKOV3 cells. The number of CTLs was significantly increased from day 7 of stimulation with the specific mixture (CpGODN, ginsenoside Rg1 and HER2/neu) (P<0.01), and plateaued on day 19. Following activation, the number of CD3 + , CD3 + CD4 + and CD3 + CD8 + cells was significantly increased (P<0.01). The lymphocyte karyotype did not change following exposure to antigen. After treatment with the specific CTL system, the number of SKOV3 cells in the experimental group was significantly reduced compared with that in the control group (P<0.01). The results of the present study suggested that two novel immune adjuvants, CpGODN and ginsenoside Rg1, could be combined with the HER2/neu antigen peptide to establish a specific CTL culture system in vitro. This system demonstrated a high antigen specificity, safety and proliferative ability, and exerted significant lethal and inhibitory effects on SKOV3 cells in vitro.

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Section: Discussionmentioning

confidence: 99%

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer

Sui

et al. 2016

Oncology Letters

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“…Several studies have demonstrated immune response but clinical benefit rate was minimal in all of these studies. The vaccination approach is not used in clinical practice nowadays [11].…”

Section: (3) Targeting the Tumor Environment (Immune Inhibitory Mechamentioning

confidence: 99%

“…To date, we have an efficacious vaccination available against the nine most important HPV types (HPV 6,11,16,18,31,33,45,52,and 58) [27]; however, despite better prevention strategies, cervical cancer is still not sufficiently manageable worldwide with a stagnating mortality rate. Most cancers in the developed world present in early FIGO stage IA1-IIA, while primary metastatic disease is uncommon.…”

Section: Cervical Cancermentioning

confidence: 99%

Immunotherapy in Gynecologic Cancers

Vetter¹,

Heinzelmann‐Schwarz²

2017

Immunotherapy - Myths, Reality, Ideas, Future

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During the last years, significant progress in the understanding of signaling pathways of immune cells has revive the field of immune therapy for cancer. In this chapter, we explain the recent immunotherapy-based strategies for the treatment of gynecological cancers including cervical cancer, endometrial cancer, ovarian cancer, and vulvar cancer. This work will mainly focus on emerging clinical data on immune checkpoint inhibitors. But also data on adoptive T cell therapies and vaccines will be presented. It is anticipated that in future biomarker-guided randomized trials will provide better approaches in terms of response and resistance to immune therapy. The use of combination therapy for gynecological cancer might be one possible approach to overcome resistance.

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“…This approach can be efficiently employed for the eradication of residual cancer cells and prevention or delay of tumor relapse (9). An example is the case of solid tumors, where antigen-specific immunotherapy has emerged as a promising approach (10)(11)(12). One of the key players in mediating immune response are the dendritic cells (DCs) as they are specialized in priming naive helper and cytotoxic T-lymphocytes and directly trigger natural killer (NK) cell function (13).…”

Section: Introductionmentioning

confidence: 99%

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

et al. 2013

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Abstract. Retinoblastoma (RB) is a challenging disease that affects mostly young children. Chemical therapy has been shown to have limitations during clinical practice, principally because of the ability of RB to become resistant to the treatment. Nevertheless, chemotherapy is still the main treatment for RB, and immunotherapy has become a promising treatment for most solid tumors with fewer side effects than traditional therapies. In this study, we explored the antitumor effects of cytokine-induced killer (CIK) cells co-cultured with dendritic cells (DCs) pulsed with complete tumor antigens (DC-Ag). Cytotoxicity and specificity were evaluated on an RB cell line (RB-Y79), on a human normal retina cell line (hTERT-RPE1) and a carboplatin-resistant RB cell line. Our results showed that CIK differentiation and cytotoxicity were enhanced by co-culturing CIKs with DC-Ag. Moreover, the co-culture improved the CIK proliferation rate by increasing IL-6 and decreasing IL-10 levels in the culture medium. Furthermore, the use of DC-Ag-CIK cells had little effect on normal retinal cells but high cytotoxicity on RB cells even on carboplatinresistant retinoblastoma cells. This is the first study showing that DC cells pulsed with the complete tumor antigen improve proliferation, differentiation and cytotoxic activity of CIKs specific not only for RB but also for the chemotherapy-resistant form of the malady. Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed.

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Antigen-specific active immunotherapy for ovarian cancer

Cited by 22 publications

References 96 publications

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer

Immunotherapy in Gynecologic Cancers

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

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