A Randomised, Parallel-group, Open-label Phase II Trial of the Immunological Effects of Three Regimens of GX301 Vaccination in Castration-resistant Prostate Cancer Patients Who Have Achieved Response or Disease Stability With First-line Chemotherapy

GX301 is an experimental therapeutic vaccine directed against human telomerase, an enzyme playing an essential role in cancer cell proliferation.
This clinical trial will test three different GX301 administration regimens in castration-resistant prostate cancer patients who have achieved response or disease stability with first-line docetaxel treatment. This is aimed at identifying an optimal vaccination regimen.
The three regimens will primarily be compared for their efficacy and safety in inducing vaccine-specific immunological responses over a period of 6 months following treatment initiation. In addition, patients will be observed for the occurrence of disease progression and for their vital status up to 24 months.

Start Date01 Nov 2014

Sponsor / Collaborator

Laboratoires Leurquin Mediolanum SA

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100 Clinical Results associated with Telomerase peptide cancer vaccine(Genovax SRL)

100 Translational Medicine associated with Telomerase peptide cancer vaccine(Genovax SRL)

100 Patents (Medical) associated with Telomerase peptide cancer vaccine(Genovax SRL)

Literatures (Medical) associated with Telomerase peptide cancer vaccine(Genovax SRL)

01 Apr 2023·Journal of Controlled Release

A mannosylated polymer with endosomal release properties for peptide antigen delivery

Article

Author: Yazdani, Omeed ; Song, Kefan ; Pun, Suzie H ; Luu, Tran ; Roy, Debashish ; Stayton, Patrick S ; Nguyen, Dinh Chuong

Peptide cancer vaccines have had limited clinical success despite their safety, characterization and production advantages. We hypothesize that the poor immunogenicity of peptides can be surmounted by delivery vehicles that overcome the systemic, cellular and intracellular drug delivery barriers faced by peptides. Here, we introduce Man-VIPER, a self-assembling (40-50 nm micelles), pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH, and facilitates endosomal release of antigens at acidic endosomal pH through a conjugated membranolytic peptide melittin. We used d-melittin to improve the safety profile of the formulation without compromising the lytic properties. We evaluated polymers with both releasable (Man-VIPER-R) or non-releasable (Man-VIPER-NR) d-melittin. Both Man-VIPER polymers exhibited superior endosomolysis and antigen cross-presentation compared to non-membranolytic d-melittin-free analogues (Man-AP) in vitro. In vivo, Man-VIPER polymers demonstrated an adjuvanting effect, induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. Remarkably, antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. As our candidate for a therapeutic vaccine, Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy.

15 Jun 2022·Science Translational MedicineQ1 · MEDICINE

Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine

Q1 · MEDICINE

Article

Author: Mangarin, Levi M. B. ; Zappasodi, Roberta ; Redmond, David ; Holmström, Morten O. ; Hobbs, Gabriela S. ; Gigoux, Mathieu ; Knudsen, Trine Alma ; Schad, Sara ; Wilkinson, Patrick ; Merghoub, Taha ; Skov, Vibe ; Mullally, Ann ; Venkatesh, Divya ; Ghosh, Arnab ; Jan, Max ; Wolchok, Jedd D. ; Hasselbalch, Hans ; George, Mariam M. ; Abdel-Wahab, Omar ; Kamaz, Baransel ; Molvi, Zaki ; Hoyos, David ; Larsen, Thomas Stauffer ; Kjær, Lasse ; Grauslund, Jacob H. ; Lindsley, R. Coleman ; Pourpe, Stephane ; Duke, William ; Met, Özcan ; Lisle, Thomas L. ; Bhardwaj, Nina ; Leventhal, Matthew J. ; Hansen, Dennis Lund ; Marneth, Anna E. ; Andersen, Mads H. ; Sepulveda, Manuel A. ; Greenbaum, Benjamin ; Rampal, Raajit ; Bozkus, Cansu Cimen ; Park, Joseph J. ; Ho, Vincent T. ; Verma, Svena ; Chan, Timothy

The majority of JAK2 V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting in a common carboxyl-terminal mutant fragment (CALR MUT ), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALR MUT -specific T cells are rare in patients with CALR MUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALR MUT MPN from two independent cohorts. We observed that MHC-I alleles that present CALR MUT neoepitopes with high affinity are underrepresented in patients with CALR MUT MPN. We speculated that this was due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifested. As a consequence of this MHC-I allele restriction, we reasoned that patients with CALR MUT MPN would not efficiently respond to a CALR MUT fragment cancer vaccine but would when immunized with a modified CALR MUT heteroclitic peptide vaccine approach. We found that heteroclitic CALR MUT peptides specifically designed for the MHC-I alleles of patients with CALR MUT MPN efficiently elicited a CALR MUT cross-reactive CD8 + T cell response in human peripheral blood samples but not to the matched weakly immunogenic CALR MUT native peptides. We corroborated this effect in vivo in mice and observed that C57BL/6J mice can mount a CD8 + T cell response to the CALR MUT fragment upon immunization with a CALR MUT heteroclitic, but not native, peptide. Together, our data emphasize the therapeutic potential of heteroclitic peptide–based cancer vaccines in patients with CALR MUT MPN.

01 Jan 2022·Journal of ImmunotherapyQ4 · MEDICINE

Cellular and Humoral Immune Responses Induced by an HLA Class I–restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer

Q4 · MEDICINE

Article

Author: Nakata, Jun ; Oka, Yoshihiro ; Tsuboi, Akihiro ; Sugiyama, Haruo ; Kanegae, Mizuki ; Nishida, Sumiyuki ; Hosen, Naoki ; Morita, Satoshi ; Morimoto, Soyoko ; Enomoto, Takayuki ; Shouq, Alzaaqi ; Fujiki, Fumihiro ; Shirakata, Toshiaki ; Kumanogoh, Atsushi ; Nakae, Yoshiki ; Nakajima, Hiroko ; Oji, Yusuke ; Yoshino, Kiyoshi ; Ohno, Satoshi ; Kimura, Tadashi ; Ueda, Yutaka

The HLA-A*24:02–restricted peptide vaccine targeting Wilms’ tumor 1 (WT1) (WT1 vaccine) is a promising therapeutic strategy for ovarian cancer; however, its efficacy varies among patients. In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events. We assessed Wilms’ tumor 1–specific cytotoxic T lymphocytes (WT1-CTLs) and Wilms’ tumor 1 peptide-specific immunoglobulin G (WT1235-IgG). After vaccination, the percentage of tetramer high-avidity population of WT1-CTLs among CD8+ T lymphocytes (%tet-hi WT1-CTL) and the WT1235-IgG titer increased significantly, although the values were extremely low or below the limit of detection before vaccination (%tet-hi WT1-CTL: 0.003%–0.103%.; WT1235-IgG: <0.05–0.077 U/mL). Patients who had %tet-hi WT1-CTL of ≥0.25% (n=6) or WT1235-IgG of ≥0.10 U/mL (n=12) had a significantly longer progression-free survival than those of patients in the other groups. In addition, an increase in WT1235-IgG corresponded to a significantly longer progression-free survival (P=0.0496). In patients with systemic inflammation, as evidenced by elevated C-reactive protein levels, the induction of tet-hi WT1-CTL or WT1235-IgG was insufficient. Decreased serum albumin levels, multiple tumor lesions, poor performance status, and excess ascites negatively influenced the clinical effectiveness of the WT1 vaccine. In conclusion, the WT1 vaccine induced antigen-specific cellular and humoral immunity in patients with refractory ovarian cancer. Both %tet-hi WT1-CTL and WT1235-IgG levels are prognostic markers for the WT1 vaccine.

100 Deals associated with Telomerase peptide cancer vaccine(Genovax SRL)

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Phase 3	ES	Laboratoires Leurquin Mediolanum SA	01 Nov 2014
Castration-Resistant Prostatic Cancer	Phase 3	IT	Laboratoires Leurquin Mediolanum SA	01 Nov 2014
Renal Cell Carcinoma	Phase 2	-	Mediolanum Farmaceutici SpA	-
Renal Cell Carcinoma	Phase 2	-	Genovax SRL	-
Kidney Neoplasms	Preclinical	IT	Genovax SRL	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EUCTR2014-000095-26-ES \| NCT02293707 (Pubmed \| Cancer Immunol Immunother)	Phase 2	Metastatic castration-resistant prostate cancer	99	GX301 (Regimen 1 (eight administrations))	wiudwqygmc(hekdgjklgr) = lnwaabsnxz fftpcqbmhe (pieilsrsyb )	-	05 Aug 2021

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