Mannan-modified adenovirus targeting TERT and VEGFR-2: A universal tumour vaccine

Wang, Ying; Zhang, Jie; Wu, Yang; Ding, Zhenyu; Luo, Xinmei; Liu, Jie; Zhong, Weiying; Deng, Guohua; Xia, Xiang-Yu; Deng, Yao; Wei, Yuquan; Jiang, Yu

doi:10.1038/srep11275

Cited by 14 publications

(8 citation statements)

References 60 publications

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“…Besides DCs, also B lymphocytes have been employed as APC for hTERT-targeted vaccination through a strategy termed “transgenic lymphocyte immunization”. In a phase I trial conducted at University of California San Diego, 15 prostate cancer patients were vaccinated with autologous transgenic B lymphocytes with pDNA encoding two hTERT peptides (p540 and p572Y), and an antigen-specific immunological response was observed in 80% of the patients [ 98 , 99 ].…”

Section: Other Vaccination Approaches Targeting Htertmentioning

confidence: 99%

Anti-Cancer Immunotherapies Targeting Telomerase

Negrini

Palma

Filaci

2020

Cancers

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Telomerase is a reverse transcriptase that maintains telomeres length, compensating for the attrition of chromosomal ends that occurs during each replication cycle. Telomerase is expressed in germ cells and stem cells, whereas it is virtually undetectable in adult somatic cells. On the other hand, telomerase is broadly expressed in the majority of human tumors playing a crucial role in the replicative behavior and immortality of cancer cells. Several studies have demonstrated that telomerase-derived peptides are able to bind to HLA (human leukocyte antigen) class I and class II molecules and effectively activate both CD8+ and CD4+ T cells subsets. Due to its broad and selective expression in cancer cells and its significant immunogenicity, telomerase is considered an ideal universal tumor-associated antigen, and consequently, a very attractive target for anti-cancer immunotherapy. To date, different telomerase targeting immunotherapies have been studied in pre-clinical and clinical settings, these approaches include peptide vaccination and cell-based vaccination. The objective of this review paper is to discuss the role of human telomerase in cancer immunotherapy analyzing recent developments and future perspectives in this field.

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Section: Other Vaccination Approaches Targeting Htertmentioning

confidence: 99%

Anti-Cancer Immunotherapies Targeting Telomerase

Negrini

Palma

Filaci

2020

Cancers

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“…The iSCRIPT cDNA synthesis kit was used to synthesise 300ng of cDNA whereas KAPA Taq PCR was used for reverse transcription PCR (RT-PCR). The real time PCR was achieved by KAPA SYBR FAST qPCR Master Mix (2X) kit from Kapa Biosystems according to the manufacturers' guidelines and the primer sequences for performing both RT-PCR and Real-Time PCR are provided in S3 Table [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][70][71][72][73][74][75][76]. For each gene, the average C(t) value was determined and was normalised to housekeeping (GAPDH) mRNA levels.…”

Section: Reverse-transcription-pcr and Real-time Pcrmentioning

confidence: 99%

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

et al. 2020

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Octamer binding transcription factor-4 (Oct4), is highly expressed in stem cells and has indispensable roles in pluripotency and cellular reprogramming. In contrast to other factors used for cellular reprogramming, a role for Oct4 outside embryonic stem cells has been elusive and highly controversial. Emerging evidence implicates Oct4 in the carcinogenic process, but the mechanism through which Oct4 may be functioning in cancers is not fully appreciated. Here, we provide evidence that Oct4 is expressed in human cervical cancer and this expression correlates with the presence of the human papillomavirus (HPV) oncogenes E6 and E7. Surprisingly, the viral oncogenes can complement exogenously provided Oct4 in reprogramming assays, providing functional validation for their ability to activate Oct4 transcription in Mouse Embryonic Fibroblasts (MEFs). To interrogate potential roles of Oct4 in cervical cancers we knocked-down Oct4 in HPV(+) (HeLa & CaSki) and HPV(-) (C33A) cervical cancer cell lines and found that Oct4 knockdown attenuated clonogenesis, only in the HPV(+) cells. More unexpectedly, cell proliferation and migration, were differentially affected in HPV(+) and HPV(-) cell lines. We provide evidence that Oct4 interacts with HPV E7 specifically at the CR3 region of the E7 protein and that introduction of the HPV oncogenes in C33A cells and human immortalised keratinocytes generates Oct4-associated transcriptional and phenotypic patterns, which mimic those seen in HPV(+) cells. We propose that a physical interaction of Oct4 with E7 regulates its activity in HPV(+) cervical cancers in a manner not seen in other cancer types.

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“…Recently, other investigators have reported that DNA vaccination based on the TEM8 gene using DCs as adjuvant resulted in the deceleration of tumor growth by enhancing anti-angiogenic effects via the induction of TEM8-specific CTLs and interferon-γ production; the effects decreased after the depletion of CD8-positive T cells. 28) Moreover, DC vaccination using adenovirus that expressed both telomerase reverse transcriptase and VEGF receptor 2 (VEGFR2) pointed to the inhibition of tumor angiogenesis by activating VEGFR2-specific CTLs.…”

Section: Discussionmentioning

confidence: 99%

Cancer Vaccine Therapy Using Tumor Endothelial Cells as Antigens Suppresses Solid Tumor Growth and Metastasis

Nomura

Hirata

Shimaoka

et al. 2017

Biological & Pharmaceutical Bulletin

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Tumor angiogenesis plays an important role in tumor growth and metastasis, with tumor cells requiring nutrients and oxygen via blood flow for their proliferation. In comparison, angiogenesis also occurs under normal physiological conditions, such as wound healing and in the formation of the corpus luteum. Herein, we report on the development of a novel dendritic cell (DC) vaccine therapy using tumor endothelial cells (TECs) derived from tumor vessels as tumor antigens. After density gradient centrifugation and the detection of angiotensin-converting enzyme activities, a TEC-rich fraction was separated from solid tumor tissues. Prophylactic or therapeutic immunization using DCs pulsed with TECs as vaccine antigens significantly suppressed solid tumor growth in a Colon-26 colorectal adenocarcinoma tumor-bearing mouse model, compared with the use of tumor cells as DC vaccine antigens. Tumor tissues showed reduced angiogenesis. However, vaccination using DCs pulsed with TECs did not inhibit physiological angiogenesis as evidenced by a wound healing assay. Additionally, in a B16/BL6 mouse melanoma lung metastasis model, DC vaccination using TECs derived not only from the same tumor tissue but from a different type of tumor also suppressed metastasis. These results thus show that cancer vaccine therapy targeting TECs is an effective therapy against angiogenesis in several types of cancer, but does not affect normal blood vessel growth.Key words tumor endothelial cell; angiogenesis; dendritic cell; vaccine; metastasis Endothelial cells that enable tumor angiogenesis are recruited from neighboring, pre-existing capillaries 1,2) by tumor angiogenesis mediators, such as vascular endothelial growth factor (VEGF),3) fibroblast growth factors, 4) and transforming growth factor, 5) in the process of tumor progression or metastasis.6,7) Newly produced blood vessels, which are constructed by tumor endothelial cells (TECs), provide oxygen and nutrients, and remove metabolic waste from tumor cells; tumor cell proliferation also depends on new blood vessel formation. 6,8) In addition, TECs in different types of cancers express common, tumor-associated antigens (TAAs), since the tumor's new blood vessels are constructed from endothelial cells of the host. In this regard, it is expected that the inhibition of angiogenesis in tumor tissue will effectively induce tumor regression for several types of cancer, compared with the direct inhibition of tumor cells themselves. In fact, several antiangiogenic agents, such as the VEGF receptor and tyrosine kinase inhibitor, sunitinib, 9) and the anti-VEGF antibody, bevacizumab, 10) are commonly applied in clinical practice today since they tend to show a survival advantage for patients. However, angiogenesis also occurs during the processes of wound healing and corpus luteum formation, 11) with the implication that the clinical application of antiangiogenic agents in cancer patients may result in damage to normal blood vessels, 12) in addition to those of the tumor. Therefore, the selective in...

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Mannan-modified adenovirus targeting TERT and VEGFR-2: A universal tumour vaccine

Cited by 14 publications

References 60 publications

Anti-Cancer Immunotherapies Targeting Telomerase

Anti-Cancer Immunotherapies Targeting Telomerase

Human papillomavirus E7 binds Oct4 and regulates its activity in HPV-associated cervical cancers

Cancer Vaccine Therapy Using Tumor Endothelial Cells as Antigens Suppresses Solid Tumor Growth and Metastasis

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