Delving into the Latest Updates on Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center) with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Synthetic peptide vaccine

Synonyms

mKRASvax, Mutant KRAS peptide vaccine with Hiltonol

Target

KRAS

Mechanism

KRAS modulators(GTPase KRas modulators), Immunostimulants

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [2]

Active Indication

Pancreatic adenocarcinomaColorectal CancerMetastatic Pancreatic Ductal Adenocarcinoma+ [6]

Inactive Indication-

Originator Organization

The Sidney Kimmel Comprehensive Cancer Center

Active Organization

The Sidney Kimmel Comprehensive Cancer Center

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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The purpose of this study is to determine the optimal dose of AGEN2373 that is safe when given in combination with balstilimab and Pancreatic GVAX Whole Cell Vaccine and evaluate the safety and clinical activity of balstilimab and AGEN2373 in combination with GVAX (Arm 1) or mKRASvax (Arm 2) in surgically resectable pancreatic adenocarcinoma.

Start Date01 Apr 2025

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+3]

NCT05254184

/ RecruitingPhase 1IIT

Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Advanced KRAS Mutated Non-Small Cell Lung Cancer

This is a single institution, Phase 1 study for patients with Stage III/IV unresectable Kirsten rat sarcoma (KRAS) mutated NSCLC to evaluate safety of the pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with polyinosinic-polycytidylic acid (poly-ICLC) adjuvant in combination with nivolumab and ipilimumab in the first line treatment setting. The primary objectives of this study are to determine the safety and feasibility of administering the KRAS peptide vaccine with poly-ICLC adjuvant in combination with nivolumab and ipilimumab. The secondary objectives are to estimate the progression free survival (PFS) of pooled mutant-KRAS long peptide vaccine with poly-ICLC adjuvant in combination with Ipilimumab + Nivolumab for the first line treatment of patients with unresectable Stage III/IV NSCLC whose tumors harbor selected KRAS mutations (KRAS glycine-to-cysteine substitution at codon 12 (G12C), KRAS glycine-to-valine substitution at codon 12 (G12V), KRAS glycine-to-Detoxglyphosate substitution at codon 12 (G12D), KRAS glycine-to-arginine substitution at codon 12 (G12A), KRAS glycine-to-Aspartic Acid "D" at codon 13 (G13D) or KRAS G12R) and to assess the impact of predicted KRAS mutations on mutant-KRAS specific T cell responses in the peripheral blood of these patients. Exploratory objectives will assess the impact of predicted KRAS mutations on mutant-KRAS specific T cell responses in the peripheral blood, as well as changes in circulating tumor deoxyribonucleic acid (ctDNA). Approximately 15 subjects will be enrolled to have 12 evaluable subjects for T cell response assessment. Safety analysis will include all enrolled patients who receive at least one dose of vaccine. The evaluable population for T cell response will consist of all patients who receive at least one dose of vaccine and have baseline and post-treatment T cell measures in the peripheral blood at 12 weeks.

Start Date01 Nov 2022

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

NCT05013216

/ RecruitingPhase 1IIT

Mutant KRAS -Targeted Long Peptide Vaccine for Patients at High Risk of Developing Pancreatic Cancer

This Phase 1 study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant for patients who have been identified to be at risk of developing pancreatic cancer.

Start Date11 Apr 2022

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+1]

100 Clinical Results associated with Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center)

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100 Translational Medicine associated with Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center)

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100 Patents (Medical) associated with Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center)

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3

Literatures (Medical) associated with Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center)

01 Oct 2023·Cell reports methods

Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses

Article

Author: Nauroth, Julie ; Larman, H Benjamin ; Johnson, Jeanette ; Huff, Amanda ; Hsiao, Meng-Hsuan ; Heumann, Thatcher ; Jayaraman, Sahana ; Jaffee, Elizabeth M ; Montagne, Janelle M ; Fertig, Elana J ; Zarif, Jelani C ; Zaidi, Neeha ; Marcisak, Emily ; Azad, Nilo ; Nirschl, Thomas R

Assays linking cellular phenotypes with T cell or B cell antigen receptor sequences are crucial for characterizing adaptive immune responses. Existing methodologies are limited by low sample throughput and high cost. Here, we present INtraCEllular Reverse Transcription with Sorting and sequencing (INCERTS), an approach that combines molecular indexing of receptor repertoires within intact cells and fluorescence-activated cell sorting (FACS). We demonstrate that INCERTS enables efficient processing of millions of cells from pooled human peripheral blood mononuclear cell (PBMC) samples while retaining robust association between T cell receptor (TCR) sequences and cellular phenotypes. We used INCERTS to discover antigen-specific TCRs from patients with cancer immunized with a novel mutant KRAS peptide vaccine. After ex vivo stimulation, 28 uniquely barcoded samples were pooled prior to FACS into peptide-reactive and non-reactive CD4⁺ and CD8⁺ populations. Combining complementary patient-matched single-cell RNA sequencing (scRNA-seq) data enabled retrieval of full-length, paired TCR alpha and beta chain sequences for future validation of therapeutic utility.

01 Nov 2019·EBioMedicineQ1 · MEDICINE

Potentiation of Kras peptide cancer vaccine by avasimibe, a cholesterol modulator

Q1 · MEDICINE

ArticleOA

Author: Wang, Li ; Palen, Katie ; You, Ming ; Johnson, Bryon ; Shoemaker, Robert H ; Zhang, Qi ; Qiao, Lifen ; Pan, Jing ; Wang, Yian ; Sei, Shizuko ; Lubet, Ronald A

BACKGROUND:

No effective approaches to target mutant Kras have yet been developed. Immunoprevention using KRAS-specific antigenic peptides to trigger T cells capable of targeting tumor cells relies heavily on lipid metabolism. To facilitate better TCR/peptide/MHC interactions that result in better cancer preventive efficacy, we combined KVax with avasimibe, a specific ACAT1 inhibitor, tested their anti-cancer efficacy in mouse lung cancer models, where Kras mutation was induced before vaccination.

METHODS:

Control of tumor growth utilizing a multi-peptide Kras vaccine was tested in combination with avasimibe in a syngeneic lung cancer mouse model and a genetically engineered mouse model (GEMM). Activation of immune responses after administration of Kras vaccine and avasimibe was also assessed by flow cytometry, ELISpot and IHC.

FINDINGS:

We found that Kras vaccine combined with avasimibe significantly decreased the presence of regulatory T cells in the tumor microenvironment and facilitated CD8+ T cell infiltration in tumor sites. Avasimibe also enhanced the efficacy of Kras vaccines target mutant Kras. Whereas the Kras vaccine significantly increased antigen-specific intracellular IFN-γ and granzyme B levels in CD8+ T cells, avasimibe significantly increased the number of tumor-infiltrating CD8+ T cells. Additionally, modulation of cholesterol metabolism was found to specifically impact in T cells, and not in cancer cells.

INTERPRETATION:

Avasimibe complements the efficacy of a multi-peptide Kras vaccine in controlling lung cancer development and growth. This treatment regimen represents a novel immunoprevention approach to prevent lung cancer.

10 Oct 2017·Oncotarget

Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine

Article

Author: Wang, Yian ; You, Ming ; Zhang, Qi ; Sei, Shizuko ; Pan, Jing ; Shoemaker, Robert H. ; Lubet, Ronald A.

Lung cancer remains the leading cause of cancer death worldwide. Mutations in KRAS are detected in up to 30% of lung cancer cases. No effective therapies specifically targeting mutant KRAS have been developed. Vaccination against KRAS mutants is one of the venues of active exploration. The present study evaluated both immunogenicity and antitumor efficacy of a newly formulated multipeptide vaccine targeting multiple epitopes of the KRAS molecule. The formulated vaccine contained top four peptides, which elicited the strongest immunologic response and showed 100% sequence homology between human and mouse. The multipeptide KRAS vaccine was tested in an inducible CCSP-TetO-KRAS^G12D mouse model, where the vaccine was administered prior to activating the mutant KRAS protein. The KRAS peptide vaccine exhibited striking efficacy, reducing tumor number and tumor burden by >80% when compared with adjuvant alone. Splenocytes collected from vaccinated animals showed a robust immunologic response to the immunizing peptides. Furthermore, in vitro stimulation of these splenocytes by the vaccinated peptides resulted in the secretion of cytokines indicative of Th1 responses but with minimal secretion of Th2-related cytokines. The multipeptide KRAS vaccine was immunogenic and efficacious in the primary prevention of KRAS-induced lung cancer, indicating that the approach potentially can be used to prevent other KRAS-driven cancers, either alone or in combination with other modalities.

100 Deals associated with Pooled mutant-KRAS peptide vaccine(The Sidney Kimmel Comprehensive Cancer Center)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic adenocarcinoma	Phase 2	US	The Sidney Kimmel Comprehensive Cancer Center	01 Apr 2025
Colorectal Cancer	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	04 Nov 2024
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	04 Nov 2024
Pancreatic Ductal Adenocarcinoma	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	04 Nov 2024
KRAS mutant Non-small Cell Lung Cancer	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	01 Nov 2022
Carcinoma in Situ	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	11 Apr 2022
Pancreatic Cyst	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	11 Apr 2022
Pancreatic Intraductal Neoplasms	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	11 Apr 2022
Pancreatic Mucinous-Cystic Neoplasm	Phase 1	US	The Sidney Kimmel Comprehensive Cancer Center	11 Apr 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05013216 (AACR2024) Manual	Phase 1	Pancreatic Cancer KRAS Mutation	15	Mutant KRAS peptide-based vaccine	yzrikefrcp(oezcsfuenf) = ebwrqlhywd vxefbyejxo (uptxeocvnn )	Positive	05 Apr 2024