INTRO

INTRO
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GemVax & KAEL

GemVax & KAEL 追求健康与幸福生活

GemVax R&D是以端粒酶衍生肽胰腺癌免疫抗癌治疗剂开发技术为基础,通过基于肽的对 多种适应症的效能证明,探索治疗剂的开发。为确保研究机构的各种研究结果的知识产 权,进行国内外专利备案及注册,记载在著名国际学术杂志上而得到认可其研究成果。

论文

Pancreatic Cancer

  • Title

    Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomized, phase 3 trial

    Summary

    1062 patients with locally advanced or metastatic pancreatic cancer were randomly assigned. The TeloVac study results showed the safety of GV1001. It also demonstrated the potential of combination between immunotherapy and chemotherapy. Authors : Gary Middleton et al., The Lancet Oncology 2014, 8: 829-840 Link
  • Title

    Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study

    Summary

    Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels (0.11 mg, 0.56 mg, 1.87 mg), in combination with GM-CSF. The treatment period was 10 weeks. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group (0.56 mg). Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- and high-dose groups. This result is underlying the clinical application dose (0.56 mg) of GV1001 in pancreatic cancer. Authors : Bernhardt SL et al. Br J Cancer. 2006, 11: 1474-82 Link
  • Title

    Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

    Summary

    A telomerase specific immune response was noted in 10 of 17 pancreatic cancer patients. These results showed that GV1001 might be used as an active immunotherapy in the treatment of cancer. Authors : Staff C et al., Int J Oncol. 2014, 3: 1293-303 Link
  • Title

    The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer

    Summary

    In TeloVac clinical trials, it was found that GV1001 might decrease MDSC, leading to the increases of patients’ immune responses through improving immunosuppressive tumor microenvironment. Authors : Nicola E. Annels et al., Cancer Immunol Immunother, 2014, 63: 175–183 Link
  • Title

    Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

    Summary

    Gem/Cap treatment group (Arm 1) in TeloVac study was investigated regarding the level of GM-CSF, IL-6, and C-reactive protein (CRP) in serum. The results showed that the anti-cancer chemotherapy induced apoptosis was not related with GV1001-specific immunogenicity. Authors : Middleton G. et al., Br. J. Cancer, 2016, 11: 510-518 Link
  • Title

    The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma

    Summary

    In PDAC (pancreatic ductal adenocarcinoma) xenograft model which is the most abundant form of pancreatic cancer, GV1001 treatment in combination with gemcitabine led to the reduction of tumor size, increased apoptosis, decreased fibrosis in conjunction with decreased TNF-alpha, IL-6, IL-1beta levels. This non- clinical study result supports the rationale for inhibition of fibrosis by PDAC. Authors : Park JK et al., Oncotarget. 2016, 7(46): 75081-75093 Link

Non-Small Cell Lung Cancer

  • Title

    Immunological factors influencing clinical outcome in lung cancer patients after telomerase peptide vaccination

    Summary

    In this study, we conducted long-term clinical follow-up for 45 patients with non-small cell lung cancer (NSCLC) evaluating vaccine therapy with GV1001 and investigated immunological factors (Treg, MDSC decrease) hypothesized to influence clinical efficacy. The results demonstrated that immune responders had increased overall survival (OS) and progression-free survival, compared to subjects without immunological response. The mean OS advantage was 54 versus 13 months. Six patients were still alive at the last clinical update (in 2015), all belonging to the immune responders. Authors : Hansen GL et al., Cancer Immunol Immunother., 2015, 12: 1609-21 Link
  • Title

    Telomerase peptide vaccination in NSCLC: a phase III trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial

    Summary

    A GV1001-specific immune response developed in 16 of 20 patients vaccinated with two telomerase peptides (GV1001 and I540) after chemoradiotherapy. Long-term immunomonitoring showed persisting responses in 13 subjects. Follow-up of four long-time survivors showed that they all harbored durable GV1001-specific T-cell memory responses. Thus, the result proposed that GV1001 might function as cancer vaccine. Authors : Brunsvig PF et al., Clin Cancer Res, 2011, 17: 6847 Link
  • Title

    Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer

    Summary

    According to the phase I/II trial reports (CTN-2000), vaccination with GV1001 is well tolerated and immunizes the majority of NSCLC patients and establishes durable T-cell memory. Authors : Brunsvig PF et al., Cancer Immunol Immunother., 2006, 55: 1553-1564 Link

Melanoma

  • Title

    Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

    Summary

    Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines. Authors : Hunger RE et al., Cancer Immunol Immunother., 2011, 60: 1553-1564 Link
  • Title

    Telomerase peptide vaccination combined with temozolomide: A clinical trial in stage IV melanoma patients

    Summary

    A GV1001-specific immune response was shown in 18 of 23 evaluated subjects (78%). The immunologic response rate is considerable compared with previous GV1001 trials without concomitant chemotherapy. The results support the general concept of combining cancer vaccination with chemotherapy. Authors : Kyte JA et al. Clin Cancer Res. 2011, 13: 4568-80 Link

HCC / CTCL / CLL / RCC

  • Title

    A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    Summary

    Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Authors : Greten TF et al., BMC Cancer., 2010, 10: 209 Link
  • Title

    Telomerase-specific GV1001 peptide vaccination fails to include objective tumor response in patients with cutaneous T cell lymphoma

    Summary

    1/6 patients with cutaneous T cell lymphoma (CTCL) acquired a GV1001-specifc T cell response. Authors : Schlapbach C et al., J. Dermatol. Sci., 2011, 2: 75-83 Link
  • Title

    Telomerase (hTERT 611-626) serves as a tumor antigen in B-cell chronic lymphocytic leukemia and generates spontaneously antileukemic, cytotoxic T cells

    Summary

    B-cell chronic lymphocytic leukemia (B-CLL) patients (6 out of 7) showed the activation of GV100-specific cytotoxic T lymphocytes (3-fold higher level compared to Ras-peptide treated group), which indicates the potential of GV1001 as B-CLL therapeutic vaccine. Authors : Kokhaei P et al., Exp Hematol. 2007, 2: 297-304 Link
  • Title

    GV1001 Induces Apoptosis by Reducing Angiogenesis in Renal Cell Carcinoma Cells Both In Vitro and In Vivo

    Summary

    It was demonstrated that GV1001 not only inhibits survival, migration, invasion and angiogenesis of renal carcinoma cells by modulation of MMP, TIMP and HIF-1alpha in vitro, but also inhibits tumor growth of renal carcinoma cells and induces apoptosis in xenograft mouse model. Authors : Kim GE et al., Urology. 2018, 113: 129-137 Link

Conference Presentation

  • Title

    Predictive cytokine biomarkers for survival in patients with advanced pancreatic cancer randomized to sequential chemoimmunotherapy comprising gemcitabine and capecitabine (GemCap) followed by the telomerase vaccine V1001 compared to concurrent chemoimmunotherapy in the TeloVac phase III trial

    Summary

    In the TeloVac phase III trial, baseline eotaxin levels of 81.02 pg/ml predicted median overall survival in GemCap chemo-immunotherapy with GV1001 (high Eotaxin, 451 days; low Eotaxin, 188 days). GemCap chemotherapy induced a fall of a distinct range of cytokines which was prevented by GV1001 given with GemCap. High eotaxin levels may predict improved survival in patients given GV1001 with GemCap. Authors : John P. Neoptolemos et al. ASCO Annual Meeting 2014
  • Title

    An exploratory phase I trial of immunochemoradiotherapy in locally advanced and borderline resectable (LA/BR) pancreatic adenocarcinoma (PC)

    Summary

    Issues related to anti-cancer immune response of Gemcitabine (Gem) and external beam radiation therapy (EBRT) in patients with locally advanced pancreatic cancer discussed. It was reported that the addition of immunotherapy (peptide vaccine + adjuvant and PDE-5 inhibitor) to systemic cytotoxic chemotherapy and concurrent chemoradiation has advantages and immunogenicity. Authors : Todd S. Crocenzi MD et al., Gastrointestinal Cancers Symposium 2013
  • Title

    A phase III randomized trial of chemoimmunotherapy comprising gemcitabine and capecitabine with or without telomerase vaccine with locally advanced or metastatic pancreatic cancer

    Summary

    OS with concurrent GemCap/GV1001 was not different from that with GemCap alone. OS with sequential GV1001 was not statistically different from GemCap alone as it did not meet the criterion for statistical significance. Authors : Middleton GW.et al., ASCO Annual Meeting Abstract 2013
  • Title

    Translational studies of the TeloVac Trial: Characterization of the Immune response to GV1001

    Summary

    Analysis of TeloVac patient PBMCs has shown a GV1001 specific response in a portion of patients. Furthermore, alanine substitution of the amino acids at positions 7 (leucine), 8 (threonine), 10 (arginine), 11 (leucine) and 12 (arginine) in GV1001 decreased the T cell response. Understanding the correlation with GV1001 peptide sequences and T cell activation may lead to targeted treatment and generation of new vaccination. Authors : Victoria Shaw et al. UK NCRI abstract 2010
  • Title

    A randomized phase lll study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable pancreatic cancer (PC)

    Summary

    365 eligible patients were divided into gemcitabine treated group and GV1001+GM-CSF treated group and compared with regard to overall survival. GV1001 did not show efficacy in sequential combination with gemcitabine in advanced pancreatic cancer. However, it suggests the possibility of further studies. Authors : T. Buanes et al., 2009 ASCO Annual Meeting
  • Title

    Treatment of advanced pancreatic cancer patients with a telomerase-peptide vaccine together with gemcitabine: A phase II clinical study

    Summary

    Six pancreatic cancer patients were divided into gemcitabine (1000 mg/m2) treated group and GV1001 (0.56 mg)+GM-CSF treated group and compared with regard to toxicity and immunogenicity. The study demonstrates that anticancer vaccination in combination with chemotherapy is safe as a treatment modality and does not aggravate the toxicity associated with the chemotherapy regimen. Immunological responses were noted in 7/12 (58%) of the patients. Authors : Aniruddha Choudhury et al. AACR Annual Meeting abstract 2007
  • Title

    Imiquimod a new adjuvant for telomerase peptide vaccine: A phase I trial in patients with inoperable pancreatic cancer

    Summary

    The present study was performed to determine safety and immunogenicity of GV1001 using imiquimod as an adjuvant. Immune responses were measured as skin reaction (DTH) and T cell proliferation assay. Immune response was detected in 5 (35.7%) of the 13 evaluable patients. And the use of Imiquimod in combination with GV1001 was well tolerated; There were no signs of toxicity. Authors : S. L. Bernhardt et al. ASCO Annual Meeting Abstract 2005
  • Title

    A phase I/II study of telomerase peptide vaccination of patients with non-small cell lung cancer

    Summary

    As a phase 1/2 clinical trial targeted at 26 patients with non-small cell lung cancer, GV1001 (0.112mg or 0.56 mg) was administered in combination with an anticancer drug HR2822 with GM-CSF. Immune responses against GV1001 were detected in 50% of patients, and a complete tumor response was observed in one patient. Authors : P. F. Brunsvig et al. ASCO Annual Meeting Abstract (2005)

Benign Prostatic Hyperplasia

  • Title

    Signal of GV1001 efficacy

    Summary

    Based on the recently completed phaseⅡclinical study for the patients with benign prostatic hyperplasia (BPH), GV1001 exhibited favorable efficacy and safety profiles suggesting the extended dosing regimen of GV1001 might be more convenient for patients than the daily administration required for most current BPH drugs. Authors : Thoma C Nat Rev Urol. 2018, Epub ahead of print Link
  • Title

    A randomised, placebo-controlled, multicentre, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia

    Summary

    The phase Ⅱ clinical study recently completed in patients with BPH (benign prostatic hyperplasia) indicated that GV1001 is effective and safe in lowering IPSS (international prostate symptom score) and reduction of prostate volume as well as providing favorable safety profiles. Authors : Moon KT et al., BJU Int. 2018, Epub ahead of print Link

Alzheimers Disease

  • Title

    Novel vaccine peptide GV1001 effectively blocks β –amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase

    Summary

    This study demonstrates that GV1001 inhibits neuronal cell death induced by beta-amlyloid which is the key pathological target of Alzheimer’s disease. These effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase. Authors : Park HH et al., Neurobiology of Aging. 2014, 35(6): 1255-1274 Link
  • Title

    Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals

    Summary

    GV1001 decreases the level of the cellular reactive oxygen species which are produced under hypoxic stress. It also increase cellular survival signal and decreases the cellular apoptotic signals, leading to enhancement of neural stem cell survival. Authors : Park HH et al., Neurotoxicology. 2016, 55: 131-141 Link

Anti-inflammatory and Cell Protection

  • Title

    The Anti-inflammatory Effect of Human Telomerase-Derived Peptide on P.gingivalis Lipopolysaccharide-Induced Inflammatory Cytokine Production and Its Mechanism in Human Dental Pulp cells

    Summary

    This study provided a mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability. It also offered a rationale for using GV1001 peptide in pulpitis treatment, vital pulpal therapy, and regenerative endodontic fields. Authors : KO YJ et al., Mediators of Inflammation, 2015, 385127 Link
  • Title

    The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production

    Summary

    In vitro study using PBMC derived from Rheumatis Arthritis patients suggests that GV1001 may be a useful anti-inflammatory peptide by downregulating pro-inflammatory cytokine production and regulation of p38 MAPK and NF-κB activation induced by ENO1 stimulation. Authors : Choi JY et al. Immune Network, 2015, 6: 291-303 Link
  • Title

    Protective effect of peptide GV1001 against renal ischemia-reperfusion injury in mice

    Summary

    Peptide GV1001 ameliorates acute renal IRI by reducing inflammation an apoptosis; promising as a potential therapeutic agent for renal IRI. Authors : Koo TY et al., Transplantation Proceedings 2014, 46: 1117-1122 Link
  • Title

    Reduction of ischemia–reperfusion injury in a rat lung transplantation model by low-concentration GV1001

    Summary

    Adding a low concentration of GV1001 to the lung preservation solution (Perfadex®) provided potential protective effects against IR injury after lung transplantation in rats. GV1001 should be considered as a promising anti-inflammatory agent for IR injury. Authors : Chang JY et al., European Journal of Cardio-Thoracic Surgery, 2016, 50(5): 972-979 Link
  • Title

    hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF‑β signaling

    Summary

    Whereas keratinocyte and fibroblast exposed to ionizing radiation underwent premature senescence and fibrosis, these deteriorating effects were ameliorated by GV1001 treatment in vitro. In a dermal fibrosis animal model, GV1001 notably reduced the fibrotic lesions by suppression of TGF-beta signaling. Authors : Chen W et al., BJU Int 2018, Epub ahead of print Link
  • Title

    Novel Peptide Vaccine GV1001 Rescues Hearing in Kanamycin/Furosemide-
    Treated Mice

    Summary

    It was proven that GV1001 treatment restores hearing function by maintaining hearing threshold and outer hair cells in cochlea in a deaf mouse model induced by kanamycin and furosemide with ototoxicity. Authors : Kim SH et al., Front Cell Neurosci. 2018, 12:3 Link
  • Title

    Tracking and protection of transplanted stem cells using a ferrocenecarboxylic
    acid-conjugated peptide that mimics hTERT

    Summary

    Fe-GV1001 (GV1001 conjugated to ferrocenecarboxylic acid) efficiently penetrated neural and mesenchymal stem cells and furthermore improved survival, proliferation and migration of stem cells under hypoxia. When Fe-GV1001-labelled stem cells were transplanted into brain of rats with stroke, the labelled cells were easily tracked by MRI imaging suggesting Fe-GV1001 can be used for in vivo tracking and improve the stem cell therapy. Authors : Park HH et al., Biomaterials. 2018, 155: 80-91 Link
  • Title

    Protective effects of GV1001 on myocardial ischemia‑reperfusion injury

    Summary

    In the non-clinical animal models of ischemic-reperfusion injury to cardiomyocyte, GV1001 treatment alleviated myocardiac injury, intracardiac hemorrhage, apoptosis, inflammatory cytokines, neutrophil infiltration, activity of myeloperoxidase. Authors : Chang JE et al., Mol Med Rep. 2017, 16(5): 7315-7320 Link
  • Title

    GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells

    Summary

    In rheumatoid arthritis animal models, GV1001 treatment improved clinical and histological joint score and decreased the level of serum IL-6 which were closely related to reduction of IFN-gamma and IL-6 after stimulation of T cell in spleen with collagen and reduction of inflammatory cytokine release by stimulating monocyte with LPS. Authors : Chen W et al., BJU Int. 2018, 45: 186-193 Link
  • Title

    Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior
    epigastric island skin flap survivability in ischemia-reperfusion injury rat model

    Summary

    In a non-clinical model of ischemia-reperfusion injury to inferior epigastric skin flap, it was proven that GV1001 treatment increases skin flap survival area and decreases the level of inflammatory cytokines, neutrophil infiltration, malondialdehyde throughout anti-oxidant effects and suppressing the inflammatory cascade. Authors : Lee YK et al., J Plast Surg Hand Surg. 2017, 51(3): 210-216 Link
  • Title

    Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90-
    dependent manner

    Summary

    It was reported that GV1001 inhibits transactivation and intracellular proliferation of HIV-1 and mediates cellular survival throughout the interaction with heat shock protein 90 (HSP90) and inhibition of NF-kB Signaling pathway. Authors : Kim H et al., Sci Rep. 2016, 6: 28896 Link

Cell Penetrating Peptide

  • Title

    Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1 a -VEGF signaling axis

    Summary

    In vivo xenograft model, GV1001 decreased tumor volume and showed anti-angiogenesis effect via anti-cancer mechanism through HIF-1α-VEGF axis and interaction with HSP70 or HSP90. Authors : Kim BK et al., Biomaterials, 2014, 1-10 Link
  • Title

    Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine

    Summary

    GV1001 was confirmed as a cell-penetrating peptide (CPP). GV1001 enters cells and interacts with intracellular HSP90 and HSP70 proteins. The cell penetrating function of GV1001 offers the applicability of GV1001 for cellular delivery of anti-cancer drugs. Authors : Lee SA et al., Biomaterials, 2013, 34: 7495-7505 Link
  • Title

    The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an
    Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide

    Summary

    It was revealed that GV1001 forming complexes with extracellular heat shock
    Protein 90(eHSP90) and 70(eHSP70) has a key role in facilitating the transport of
    molecular cargo such as proteins, DNA, siRNA macromolecules into cellular
    cytosol as cell-penetrating peptide (CPPs).
    Authors : Km H et al., Int J Mol Sci. 2016, 17(12) 논문 자세히보기
专利

GV1001™ 主要用途专利

GemVax & KAEL 肽制剂研究开发专利保有现状

GV1001™用途专利
备案及注册
国内 国外 小计 国家
抗癌 (RIAVAX™) 3 19 22 韩国,美国,日本,中国,欧洲外多国家
抗炎 4 40 44
抗病毒 1 5 6
细胞穿透性 (CPP) 3 6 9
前列腺增生症 (BPH) 2 15 17
阿尔茨海默氏 4 15 19
其他 22 55 77
合计 39 155 194
新肽物质专利
备案及注册
国内 国外 小计 国家
抗癌 1 54 55 韩国,美国,日本,中国,欧洲外多国家.
抗炎 4 44 48
抗氧化 1 1 2
细胞穿透性 (CPP) 4 33 37
其他 8 52 60
合计 18 184 202
其他专利 国内 国外 小计 国家
DNA 疫苗 80 80 韩国,美国,日本,中国,欧洲外多国家.
细胞疫苗 45 45
合计 125 125