Abstract
To investigate the therapeutic potential of human embryonic stem cells (hESCs) as a vaccine to induce an immune response and provide antitumor protection in a rat model. Cross-reactivity of antigens between hESCs and tumour cells was screened by immunohistochemistry. Fischer 344 rats were divided into 7 groups, with 6 rats in each, immunized with: Group 1, hESC; Group 2, pre-inactivated mitotic NuTu-19; Group 3 PBS; Group 4, hESC; Group 5, pre-inactivated mitotic NuTu-19; Group 6, PBS; Group 7, hESC only. At 1 (Groups 1-3) or 4 weeks (Groups 4-6) after the last vaccination, each rat was challenged intraperitoneally with NuTu-19. Tumor growth and animal survival were closely monitored. Rats immunized with H9 and NuTu- 19 were tested by Western blot analysis of rat orbital venous blood for cytokines produced by Th1 and Th2 cells. hESCs presented tumour antigens, markers, and genes related to tumour growth, metastasis, and signal pathway interactions. The vaccine administered to rats in Group 1 led to significant antitumor responses and enhanced tumor rejection in rats with intraperitoneal inoculation of NuTu-19 cells compared to control groups. In contrast, rats in Group 4 did not display any elevation of antitumour responses. Western blot analysis found cross-reactivity among antibodies generated between H9 and NuTu-19. However, the cytokines did not show significant differences, and no side effects were detected. hESC-based vaccination is a promising modality for immunotherapy of ovarian cancer.
Highlights
The history of immunizing animals with fetal tissues to generate an antitumor response dates back a century ago (Brewer et al, 2009)
It was found that cancer stem cells (CSCs) and embryonic stem cells (ESCs) shared similar cell surface markers and antigens not presented by adult tissues, which played a part in metastasis, angiogenesis and increased chemoradiotherapy resistance in cancer (Field et al, 2010; Kee et al, 2012; Lopez et al, 2012), so immune response against ESCs would cross-react with cancer cells (Li et al, 2009)
Human ESCs present tumor antigens Immunohistochemical methods were used to screen tumor markers in H9 cell line, we found that several oncogenes, tumor suppressor genes, and metastasisrelated genes had high expression in human embryonic stem cells (hESCs)
Summary
The history of immunizing animals with fetal tissues to generate an antitumor response dates back a century ago (Brewer et al, 2009). Subsequent reports supported the concept that vaccination with embryonic materials could generate cancer-specific immunity and protect animals from transplantable and chemically induced tumors. Li et al (2009) demonstrated the capacity of human ES cells to effectively immunize against murine colon cancer for the first time This was further supported by three additional studies that embryonic stem cells had successfully provided activation of antitumor immunity, leading to impressive suppression of proliferation and development of malignant colon tumors and lung cancer (Dong et al, 2010; Mocan and Iancu, 2011; Yaddanapudi et al, 2012)
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