A Multicenter Randomized Phase IIb Efficacy Study of Vx-001, a Peptide-Based Cancer Vaccine as Maintenance Treatment in Advanced Non–Small-Cell Lung Cancer: Treatment Rationale and Protocol Dynamics

Georgoulias, Vassilis; Douillard, Jean-Yves; Khayat, David; Manegold, Christian; Rosell, Rafael; Rossi, Antonio; Menez-Jamet, Jeanne; Iche, Marina; Kosmatopoulos, Kostas; Gridelli, Cesare

doi:10.1016/j.cllc.2013.02.001

Cited by 23 publications

(15 citation statements)

References 20 publications

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“…After removing duplicate entries, 462 studies were evaluated for inclusion based on the title and/or abstract, after which 114 potentially relevant studies were included for full-text examination; the majority of excluded studies were reviews or animal studies and 6 studies were not reported in English. From the 114 studies, full-text was unavailable for one study 13 , 2 studies were duplicates published under different titles 14,15 , one study only described the study design 16 and 6 studies did not report safety, tolerability and/or toxicity results 7,[17][18][19][20][21] . These together with 11 case reports [22][23][24][25][26][27][28][29][30][31][32] and 2 letters to the editor were excluded 33,34 .…”

Section: Resultsmentioning

confidence: 99%

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Doorn¹,

Liu²,

Huckriede³

et al. 2015

Human Vaccines & Immunotherapeutics

111

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Section: Resultsmentioning

confidence: 99%

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Doorn¹,

Liu²,

Huckriede³

et al. 2015

Human Vaccines & Immunotherapeutics

111

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“…Another vaccine called Vx001 is a cryptic peptide (functional peptides hidden in protein structures)-based vaccine containing hTERT amino acid sequence YLFFYRKSV. The vaccine shows high affinity for HLA class I and has demonstrated a significant immune response rate in cancer patients [ 75 , 76 ]. A dendritic-cell-based vaccine, GRNVAC1, consists of mature autologous dendritic cells transduced with mRNA encoding hTERT and LAMP1.…”

Section: Anti-telomerase Immunotherapeuticsmentioning

confidence: 99%

Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies

et al. 2016

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Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized.

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“…The estimated median overall survival (OS) was 30 months for patients with immunological responses vs. four months for those without immunological responses [ 174 ]. Currently, Vx-001 development is ongoing in a randomized phase IIb trial to evaluate efficacy and survival rate at 12 months in patients with NSCLC [ 142 ].…”

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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A Multicenter Randomized Phase IIb Efficacy Study of Vx-001, a Peptide-Based Cancer Vaccine as Maintenance Treatment in Advanced Non–Small-Cell Lung Cancer: Treatment Rationale and Protocol Dynamics

Cited by 23 publications

References 20 publications

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies

Telomere and Telomerase Therapeutics in Cancer

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