Delving into the Latest Updates on Gastric cancer vaccine(OncoTherapy Science, Inc.) with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Therapeutic vaccine

Synonyms

Gastric cancer vaccine, OTSGC-A24

Target

VEGFR1 x VEGFR2

Action

antagonists

Mechanism

VEGFR1 antagonists(Vascular endothelial growth factor receptor 1 antagonists), VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication-

Inactive Indication

Advanced Gastric AdenocarcinomaAdvanced gastric carcinomaMetastatic Gastric Carcinoma+ [1]

Originator Organization

OncoTherapy Science, Inc.

Active Organization-

Inactive Organization

National University Hospital

Bristol Myers Squibb Co.

OncoTherapy Science, Inc.

License Organization

Nobelpharma Co., Ltd.

OncoTherapy Science, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo.

METHODS:

Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope). Cytokines induced by the vaccines in vitro were assessed by ELISA. A tumor challenge model was created by treating BALB/c mice on either a prophylactic or therapeutic vaccination schedule. 5-FU was simultaneously applied to mice in the combination treatment group. CTL and ADCC activities were determined by the LDH method, while CD3⁺/CD8⁺, CD3⁺/CD4⁺ T cells and MDSCs were evaluated by flow cytometry.

RESULTS:

In vitro, rapid TNF-α and IL-12 inductions occurred in BMDCs treated with the vaccines. In vivo, among all the vaccines tested, T7 - MB most effectively reduced EAC tumor burdens and induced CTLs, antibodies and ADCC activity in BALB/c mice. Immunization with T7 - MB in combination with 5-FU chemotherapy reduced tumor sizes and extended long-term survival rates, mainly by improving T cell responses, including CTLs, CD3⁺/CD8⁺ and CD3⁺/CD4⁺ T cells. 5-FU also enhanced the T7 - MB efficiency by reversing immunosuppressive factors, i.e., MDSCs, which could not be validly inhibited by the vaccines alone. In addition, T7 - MB repressed tumor growth and immune tolerance when the therapeutic schedule was used, although the effects were weaker than those achieved with either T7 - MB alone or in combination with 5-FU on the prophylactic schedule.

CONCLUSIONS:

A novel effective gastric cancer vaccine was constructed, and the importance of branched multiple antigen peptides and chemical conjugation to vaccine design were confirmed. The synergistic effects and mechanisms of T7 - MB and 5-FU were also established, observing mainly T cell activation and MDSC inhibition.

01 Dec 2018·BMC cancerQ2 · MEDICINE

A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer

Q2 · MEDICINE

ArticleOA

Author: Kim, Chan ; Mimura, Kousaku ; Katsuda, Masahiro ; Kim, Hyo Song ; Sundar, Raghav ; Kua, Ley-Fang ; Rha, Sun Young ; Kono, Koji ; Yamaue, Hiroki ; Yong, Wei Peng

BACKGROUND:

We conducted a phase I/Ib, open-label, single-arm trial to assess the safety, tolerability and optimal scheduling regimen of OTSGC-A24 cancer vaccine in patients with advanced gastric cancer.

METHODS:

Patients with advanced gastric cancer with HLA-A*24:02 haplotype were included in this study. OTSGC-A24 was administered at 1 mg in 3-weekly (3w), 2-weekly (2w), and weekly (1w) cohorts to evaluate the safety, immunological response and schedule. Based on the highest specific cytotoxic T lymphocyte (CTL) induction rate at 4 weeks, using the ELISPOT test, cohorts were expanded to define the optimal dosing schedule for OTSGC-A24.

RESULTS:

In this study, 24 advanced gastric cancer patients with HLA-A*24:02 haplotype were enrolled and treated in 3 cohorts (3w cohort: 3; 2w cohort: 11 and 1w cohort: 10 patients). The most common adverse events were decreased appetite (29%), diarrhea (21%), myalgia (25%). The most common treatment-related adverse event was injection site erythema (25%). No dose-limiting toxicities were observed in any cohort and OTSGC-A24 was well tolerated. Positive CTL responses after vaccination were observed in 15 patients (75%) at 4 weeks: 3w cohort (33%), 2w cohort (88%), 1w cohort (78%). At 12 weeks, 18 patients had responded (90%); 3w cohort (100%), 2w cohort (100%), 1w cohort (78%). The best radiological was stable disease (40%). Median progression free survival was 1.7 months (95% CI: 1.4 to 3.5) and median overall survival was 5.7 months (95% CI 3.8 to 8.6).

CONCLUSIONS:

OTSGC-A24 combined peptide cancer vaccine was well tolerated. Significant responses in CTL were observed and the recommended phase 2 dose is 1 mg OTSGC-A24 sub-cutaneous, every 2 weeks. Although no radiological response was observed, a respectable overall survival was achieved, consistent with other immunotherapy agents being investigated in gastric cancer.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT01227772 , Date registered: 21 Oct 2010.

01 May 2001·Zhonghua zhong liu za zhi [Chinese journal of oncology]

[Immunogenicity of phage-displayed tumor antigen-mimic peptide].

Article

Author: Xu, H ; Ma, F ; Xu, L

OBJECTIVE:

To determine the immunogenicity of phage-displayed tumor antigen-mimic peptide, and to lay experimental foundation for the development of gastric cancer vaccine.

METHODS:

Based on previous studies, two phage-displayed peptide libraries were screened and 12 and 30 positive phage clones obtained from two libraries respectively. All the positive phages were purified and used them to immunize Balb/c mice. The immune serum was screened by immunohistochemical with tissue sections of human gastric cancer expressing MG7 antigen. The result was further confirmed by fluorescence labeling and ELISA.

RESULTS:

Through immunohistochemical screening of immune sera with tissue sections of human gastric cancer, one phage displayed mimic peptide was able to elicit production of antibody specific for human gastric cancer.

CONCLUSION:

The result demonstrates that it is possible to develop tumor vaccine based on antigen epitope mimic peptide with immunogenicity.

100 Deals associated with Gastric cancer vaccine(OncoTherapy Science, Inc.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced gastric carcinoma	Phase 2	United States	National University Hospital	01 Nov 2010
Advanced gastric carcinoma	Phase 2	Japan	National University Hospital	01 Nov 2010
Advanced gastric carcinoma	Phase 2	Singapore	National University Hospital	01 Nov 2010
Stomach Cancer	Phase 2	-	OncoTherapy Science, Inc.	-
Stomach Cancer	Phase 2	-	Bristol Myers Squibb Co.	-
Advanced Gastric Adenocarcinoma	Phase 1	Singapore	Bristol Myers Squibb Co.	21 Feb 2019
Metastatic Gastric Carcinoma	Phase 1	Singapore	Bristol Myers Squibb Co.	21 Feb 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03784040 (da VINci, ESMO2022) Manual	Phase 1	Metastatic gastric adenocarcinoma Second line HLA A*24:02 subtype	25	OTSGC-A24 1mg+nivolumab 240mg	miptwspzun(bnuwzdxvrt) = injection site reactions (n=5 [27.8%], ≥G3=0), fatigue (n=5 27.8%], ≥G3=0), rash (n=5 [27.8%], ≥G3=1), transaminitis (n=3 [16.7%], ≥G3=0), fever (n=3 [16.7%], ≥G3=0) pcbiyookzo (enlgtfaomm )	Positive	10 Sep 2022