Immunogenicity of GX301 cancer vaccine: Four (telomerase peptides) are better than one

Fenoglio, Daniela; Parodi, Alessia; Lavieri, Rosa; Kalli, Francesca; Ferrera, Francesca; Tagliamacco, Augusto; Guastalla, Andrea; Lamperti, Maria Giuseppina; Filaci, Gilberto

doi:10.1080/21645515.2015.1012032

Cited by 27 publications

(21 citation statements)

References 36 publications

(42 reference statements)

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“…Direct activation using TERT derived peptides-GX-301: GX-301 is composed of four TERT-derived peptides, p540–548, p611–626, p672–686, and p766–780 shown to elicit T cell activation and cytokine release by ELISpot and FACS, and these immune responses were augmented when all four peptides were used in combination [ 175 ]. In a small phase I/II clinical trial in patients with prostate and renal cell carcinoma, intra-dermal GX-301 injection was well tolerated.…”

Section: Telomere and Telomerase Therapeuticsmentioning

confidence: 99%

Telomere and Telomerase Therapeutics in Cancer

Goldkorn

2016

Genes

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Telomerase is a reverse transcriptase capable of utilizing an integrated RNA component as a template to add protective tandem telomeric single strand DNA repeats, TTAGGG, to the ends of chromosomes. Telomere dysfunction and telomerase reactivation are observed in approximately 90% of human cancers; hence, telomerase activation plays a unique role as a nearly universal step on the path to malignancy. In the past two decades, multiple telomerase targeting therapeutic strategies have been pursued, including direct telomerase inhibition, telomerase interference, hTERT or hTERC promoter driven therapy, telomere-based approaches, and telomerase vaccines. Many of these strategies have entered clinical development, and some have now advanced to phase III clinical trials. In the coming years, one or more of these new telomerase-targeting drugs may be expected to enter the pharmacopeia of standard care. Here, we briefly review the molecular functions of telomerase in cancer and provide an update about the preclinical and clinical development of telomerase targeting therapeutics.

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Section: Telomere and Telomerase Therapeuticsmentioning

confidence: 99%

Telomere and Telomerase Therapeutics in Cancer

Goldkorn

2016

Genes

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“…A potent immune response needs both CD4+ and CD8+ T cell responses [26]. Combined epitopes generate [27]. At least four epitopes were needed for a PPC > 95%.…”

Section: Discussionmentioning

confidence: 99%

West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage

Waller

Reche

Flower

2020

Journal of Immunology Research

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West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%.

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“…Few tumor vaccines have been listed, most of which are in fundamental research or clinical trials. Although vaccine industry is just emerging, it has shown very strong momentum of development [ 43 ]. The advantage of tumor vaccines is that it could produce long-term immune memory and more durable antitumor effect.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Key Fields and Their Key Technical Points of Oncology by Patent Analysis

2015

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BackgroundThis paper aims to identify the key fields and their key technical points of oncology by patent analysis.Methodology/Principal FindingsPatents of oncology applied from 2006 to 2012 were searched in the Thomson Innovation database. The key fields and their key technical points were determined by analyzing the Derwent Classification (DC) and the International Patent Classification (IPC), respectively. Patent applications in the top ten DC occupied 80% of all the patent applications of oncology, which were the ten fields of oncology to be analyzed. The number of patent applications in these ten fields of oncology was standardized based on patent applications of oncology from 2006 to 2012. For each field, standardization was conducted separately for each of the seven years (2006–2012) and the mean of the seven standardized values was calculated to reflect the relative amount of patent applications in that field; meanwhile, regression analysis using time (year) and the standardized values of patent applications in seven years (2006–2012) was conducted so as to evaluate the trend of patent applications in each field. Two-dimensional quadrant analysis, together with the professional knowledge of oncology, was taken into consideration in determining the key fields of oncology. The fields located in the quadrant with high relative amount or increasing trend of patent applications are identified as key ones. By using the same method, the key technical points in each key field were identified. Altogether 116,820 patents of oncology applied from 2006 to 2012 were retrieved, and four key fields with twenty-nine key technical points were identified, including “natural products and polymers” with nine key technical points, “fermentation industry” with twelve ones, “electrical medical equipment” with four ones, and “diagnosis, surgery” with four ones.Conclusions/SignificanceThe results of this study could provide guidance on the development direction of oncology, and also help researchers broaden innovative ideas and discover new technological opportunities.

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Immunogenicity of GX301 cancer vaccine: Four (telomerase peptides) are better than one

Cited by 27 publications

References 36 publications

Telomere and Telomerase Therapeutics in Cancer

Telomere and Telomerase Therapeutics in Cancer

West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage

Identification of the Key Fields and Their Key Technical Points of Oncology by Patent Analysis

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