PEP-CMV Component A

PEP-CMV: Component A is a peptide vaccine developed for immunotherapy against brain tumors. It consists of a synthetic long peptide (SLP) of 26 amino acid residues derived from human cytomegalovirus (CMV) pp65 antigen. This peptide is designed to activate the immune system to target CMV antigens that are expressed in certain brain tumors but not in normal brain tissue. ## Composition and Mechanism PEP-CMV: Component A is administered as a stable water:oil emulsion in Montanide ISA 51, which serves as an adjuvant to enhance the immune response[1][9]. The synthetic long peptide encodes multiple potential class I, class II, and antibody epitopes across several haplotypes, allowing it to stimulate a broad immune response[1][7]. The vaccine works by targeting the human cytomegalovirus (CMV) antigen pp65, which is ubiquitously expressed in high-grade glioma (HGG) and medulloblastoma but not in adjacent brain tissue[5]. By stimulating an immune response against these CMV antigens, the vaccine aims to help the body fight off tumor cells in the patient's brain[3]. ## Clinical Development PEP-CMV is currently in Phase 2 clinical trials. A first-in-human Phase 1 trial (NCT03299309) has already been completed, which assessed the safety and feasibility of the vaccine in children and young adults with recurrent medulloblastoma and high-grade glioma[5]. The results from this trial showed that PEP-CMV is well-tolerated and elicits an antigen-specific immune response in heavily pretreated, multiply recurrent patients with a 12-month overall survival of 26.6%[5]. A multi-institutional Phase 2 trial (NCT05096481) is currently recruiting participants. This study aims to evaluate whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in: - Pediatric patients with newly-diagnosed high-grade glioma (HGG) - Diffuse intrinsic pontine glioma (DIPG) - Recurrent medulloblastoma (MB)[1][9] The trial is being conducted at multiple sites including Nationwide Children's Hospital in Columbus, Ohio; Children's Hospital of Philadelphia; Texas Children's Hospital in Houston; and Seattle Children's Hospital[1]. ## Administration Protocol In clinical trials, the vaccine administration protocol typically includes: 1. A single 5-day course of temozolomide to induce lymphopenia 2. Tetanus/diphtheria toxoid site preconditioning to promote dendritic cell migration 3. PEP-CMV administered intradermally in the groin every two weeks for 3 doses, then monthly[5] This approach is designed to optimize the immune response to the vaccine. The development of PEP-CMV represents an important advancement in immunotherapy for pediatric brain tumors, offering a potential new treatment option for conditions with limited therapeutic alternatives.

Other names

Component A