IDH1R132H peptide vaccine

The IDH1R132H peptide vaccine is a therapeutic cancer vaccine specifically designed to target the IDH1R132H mutation, which is a common mutation found in gliomas and other tumors. This vaccine represents an innovative approach to treating IDH1-mutated cancers by stimulating the immune system to recognize and attack cancer cells harboring this specific mutation. ## Development and Clinical Testing The vaccine was initially established in MHC-humanized mouse models and has progressed through clinical testing. The NOA-16 trial was a significant Phase I first-in-human multicenter clinical trial conducted by the Neurooncology Working Group (NOA) of the German Cancer Society[1]. This trial enrolled 33 patients with IDH1R132H-mutated WHO grade III-IV gliomas, with 32 patients receiving treatment[1]. The trial was completed in 2017 and demonstrated both safety and immunogenicity when combined with standard of care treatments (radiation, alkylating chemotherapy, or both)[1]. The vaccine has shown promising results, with immune responses observed in 93.3% of treated patients in the NOA-16 trial[1]. These responses were either transient or sustained, indicating the vaccine's ability to effectively target the IDH1R132H neoepitope. ## Mechanism and Formulation The IDH1R132H peptide vaccine targets a tumor-specific neoepitope created by the IDH1R132H mutation. This mutation is particularly significant because: 1. It is a disease-defining mutation in oligodendrogliomas and astrocytomas 2. It creates a mutant protein with neomorphic enzymatic activity (excessive R-2-HG production) 3. The neoepitope is expressed uniformly in all tumor cells and typically preserved in recurrent tumors[1] The vaccine formulation consists of: - A peptide spanning the mutated region of IDH1R132H - In some trials, it's administered as a 20-mer peptide encompassing the IDH1R132H-mutated region emulsified in Montanide[8] - Often administered with immune adjuvants such as GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) mixed with Montanide ISA 51[7] - Some protocols include topical imiquimod (Aldara) to enhance immune response[8] ## Ongoing Research The AMPLIFY-NEOVAC trial is a randomized, 3-arm multicenter Phase I trial designed to assess the safety, tolerability, and immunogenicity of the IDH1-vac vaccine combined with immune checkpoint inhibitors[1][5]. This trial is enrolling patients with IDH1R132H-mutated gliomas with unfavorable molecular profiles who have progressed after radiotherapy and alkylating chemotherapy[5]. The trial structure includes: - Arm 1: IDH1R132H peptide vaccine alone - Arm 2: IDH1R132H peptide vaccine combined with Avelumab (anti-PD-L1 antibody) - Arm 3: Avelumab alone[5] Another trial (NCT02193347) is investigating the vaccine in combination with temozolomide for recurrent Grade II glioma[7]. The long-term follow-up data from earlier trials supports conducting randomized clinical trials of the IDH1-vac in patients with newly diagnosed IDH1-mutant gliomas, with recommendations for a booster treatment regimen[2]. ## Development Status The IDH1R132H peptide vaccine is currently in Phase I clinical trials for malignant astrocytomas and other IDH1R132H-mutated gliomas[6][8]. It has shown promising safety profiles and preliminary evidence of efficacy, with one Phase I trial reporting stable disease in 87.5% (28/32) of patients with malignant astrocytoma harboring IDH1R132H[6]. The vaccine represents an important advancement in targeted immunotherapy for brain tumors, particularly those with the IDH1R132H mutation, which is a frequent founder event in gliomas and other cancers[4].

Other names

IDH1-vac vaccineIDH-1-vac vaccineIDH 1-vac vaccine