Combination of p53-DC vaccine and rAd-p53 gene therapy induced CTLs cytotoxic against p53-deleted human prostate cancer cells in vitro

Saito, Hiroki; Kitagawa, Koichi; Yoneda, Tomomi; Fukui, Yuka; Fujsawa, M; Bautista, Diosdado S.; Shirakawa, Toshiro

doi:10.1038/cgt.2017.21

Cited by 17 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Norcantharidin could induce apoptosis and inhibit proliferation of Tregs and its mechanism is probably associated with Vaccine therapy is an important and effective approach in treating many malignancies. 19,20 Several published studies have shown that GM-CSF-modified cell vaccines could induce effective antitumor immunity. 19,21 Granulocyte macrophage colony-stimulating factor plays a major role in maturation of DCs and activation of CD4 + and CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Norcantharidin enhances antitumor immunity of GM‐CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells

Zhang

Shi

et al. 2018

Cancer Science

View full text Add to dashboard Cite

Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cell vaccine. The results of the in vitro study showed that NCTD induced apoptosis and inhibited proliferation of regulatory T cells (Tregs). Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in a pro‐apoptotic effect. The results of the in vivo study showed that more tumor‐infiltrating Tregs existed within peripheral blood and tumor tissue after treatment with the vaccine. Adding NCTD to vaccine treatment could decrease the number of tumor‐infiltrating Tregs and increase the number of CD4+ and CD8+ T cells. Combination therapy with NCTD and vaccine was more effective in inhibiting tumor growth than the vaccine alone. In general, this is the first report that NCTD could induce apoptosis of Tregs and enhance the vaccine‐induced immunity.

show abstract

Section: Discussionmentioning

confidence: 99%

Norcantharidin enhances antitumor immunity of GM‐CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells

Zhang

Shi

et al. 2018

Cancer Science

View full text Add to dashboard Cite

show abstract

“…102 The experimental data for Ad-p53-dependent activation of lymphokine activated killer cells (LAK) and cytotoxic T lymphocytes (CTL) provide some insight into the mechanism by which Gendicine may enhance immunotherapy. 103,104 Combination with TCM. Gendicine has been combined with TCM for the treatment of cancer.…”

Section: Use Of Gendicine To Treat Head and Neck Cancermentioning

confidence: 99%

“…This suggests that combination therapy with p53-DC vaccination and Ad-p53 gene therapy together may represent a new paradigm for the treatment of metastatic castration resistant prostate cancer. 103 The chemotherapy-augmenting effects of Gendicine may act by reversing multidrug resistance (MDR) through regulation of autophagy. p53 is thought to contribute to lung cancer cell radiosensitivity by regulating autophagy and apoptosis.…”

Section: Enhancing Other Therapiesmentioning

confidence: 99%

The First Approved Gene Therapy Product for Cancer Ad-p53(Gendicine): 12 Years in the Clinic

et al. 2018

View full text Add to dashboard Cite

Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004. Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions. Based on 12 years of commercial use in >30,000 patients, and >30 published clinical studies, Gendicine has exhibited an exemplary safety record, and when combined with chemotherapy and radiotherapy has demonstrated significantly higher response rates than for standard therapies alone. In addition to head and neck cancer, Gendicine has been successfully applied to treat various other cancer types and different stages of disease. Thirteen published studies that include long-term survival data showed that Gendicine combination regimens yield progression-free survival times that are significantly longer than standard therapies alone. Although the p53 gene is mutated in >50% of all human cancers, p53 mutation status did not significantly influence efficacy outcomes and long-term survival rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements, and 169,571 vials (1.0 × 10 vector particles per vial) have been used to treat patients. No serious adverse events have been reported, except for vector-associated transient fever, which occurred in 50-60% of patients and persisted for only a few hours. The manufacturing accomplishments and clinical experience with Gendicine, as well as the understanding of its cellular mechanisms of action and implications, could provide valuable insights for the international gene therapy community and add valuable data to promote further developments and advancements in the gene therapy field.

show abstract

“…In some studies, replication-deficient or replication-competent adenoviral vectors were used to deliver transgenes, which express a tumor suppressor protein or cytotoxic/suicide protein that induces cell cycle arrest or a death cascade [176,177]. More than 50% of cancers have a mutation in tumor suppressor gene p53.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Adenoviral Vector-Based Vaccines and Gene Therapies: Current Status and Future Prospects

Singh¹,

Kumar²,

Agrawal³

2019

Adenoviruses

View full text Add to dashboard Cite

Adenoviruses are one of the most genetically diverse DNA viruses and cause non-lifethreatening infections in the ocular, respiratory, or gastrointestinal epithelium of a diverse range of hosts. Adenoviruses are excellent vectors for delivering genes or vaccine antigens to the target host tissues and are being tested in several vaccine and gene therapy studies. Adenovirus-based vectors offer several advantages over other viral vectors such as broad range of tissue tropism, well-characterized genome, ease of genetic manipulation including acceptance of large transgene DNA insertions, inherent adjuvant properties, ability to induce robust transgene-specific T cell and antibody responses, non-replicative nature in host, and ease of production at large scale. However, several studies have highlighted major drawbacks to using adenovirus as vaccine and gene therapy vectors. These include pre-existing immunity in humans, inflammatory responses, sequestering of the vector to liver and spleen, and immunodominance of the vector genes over transgenes. In the same vein, recently discovered protein sequence homology and heterologous immunity between adenoviruses and hepatitis C virus have significant implications in the use of adenoviral vectors for vaccine development, especially for hepatitis C virus. This chapter focuses on the current scope and challenges in using adenoviral vector-based vaccines and gene therapies.

show abstract

Combination of p53-DC vaccine and rAd-p53 gene therapy induced CTLs cytotoxic against p53-deleted human prostate cancer cells in vitro

Cited by 17 publications

References 39 publications

Norcantharidin enhances antitumor immunity of GM‐CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells

Norcantharidin enhances antitumor immunity of GM‐CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells

The First Approved Gene Therapy Product for Cancer Ad-p53(Gendicine): 12 Years in the Clinic

Adenoviral Vector-Based Vaccines and Gene Therapies: Current Status and Future Prospects

Contact Info

Product

Resources

About