Found 1 Presentation For Request "1005P"
1005P - A new platform of personalized neoantigen cancer vaccines directed by checkpoint inhibitor antibodies to improve cancer immunity
- Yuji Mishima (Kawasaki, Japan)
Abstract
Background
Personalized neoantigen vaccines have demonstrated robust tumor-specific immunity and preliminary evidence to cure patients with melanoma and other cancers. To improve the efficacy of personalized cancer vaccine, we herein, describe a novel vaccine platform using neoantigen peptides that contain a high affinity binding motif for dendritic cells (DCs)-targeting antibodies.
Methods
We developed peptide vaccine that consists of neoantigen-epitope and an IgG binding domain. The peptides form a divalent peptide complex per antibody molecule by simply mixing with therapeutic antibodies in physiological condition. Initially, we selected ovalbumin (OVA) as a model antigen and evaluated the efficacy of this vaccine format in combination with dendritic cell (DC)-targeting antibodies in vivo. Next, we generated series of neoantigen peptides in both murine and human origins using in-house bioinformatic algorithms and evaluate the advantages of this vaccine platform.
Results
DC-targeting OVA vaccine showed robust T-cell response and anti-tumor activity when combined with anti-CD40 agonistic antibody or atezolizumab compared with a peptide vaccine alone. In addition, preclinical evaluation of neoantigen vaccines from murine tumor showed improved CD8+ T-cell response to even for epitopes that do not respond with a conventional long peptide vaccine. Finally, using HLA-transgenic mice, we also confirmed the advantage of the new vaccine platform to patient-derived neoantigen epitopes.
Conclusions
Our new platform of cancer vaccines dramatically improved T-cell response and anti-tumor activity over conventional vaccine format. We demonstrated that the reinforcement of vaccine potency was achieved not only by the function of the antibodies on DCs but mainly by the increased antigen delivery to DCs. Enhanced T-cell response was more remarkable in CD8+ T-cells, suggesting that new platform vaccine facilitates antigen cross-presentation. The neoantigen models demonstrated that the new vaccine format works for multiple antigenic peptides. Thus, our new platform of cancer vaccines provides a critical solution to enhance personalized neoantigen vaccines.
Legal entity responsible for the study
Brightpath Biotherapeutics Co. Ltd.
Funding
Brightpath Biotherapeutics Co. Ltd.
Disclosure
Y. Mishima: Financial Interests, Personal, Full or part-time Employment: Brightpath Biotherapeutics. F. Isoda: Financial Interests, Personal, Full or part-time Employment: Brightpath Biotherapeutics. N. Matsumoto: Financial Interests, Personal, Full or part-time Employment: Brightpath Biotherapeutics. K. Hiranuka: Financial Interests, Personal, Full or part-time Employment: Brightpath Biotherapeutics. T. Yamada: Financial Interests, Personal, Full or part-time Employment: Brightpath Biotherapeutics. T. Nakatsura: Financial Interests, Institutional, Research Grant: Brightpath Biotherapeutics Co., Ltd. N. Nakamura: Financial Interests, Personal, Full or part-time Employment: BrightPath Biotherapeutics. All other authors have declared no conflicts of interest.