2. Academic Validation
  3. Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles

Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles

  • J Extracell Vesicles. 2022 Aug;11(8):e12243. doi: 10.1002/jev2.12243.
Xiao Xiong 1,  Xiurong Ke 2 3,  Lu Wang 1,  Yusheng Lin 1 3 4,  Shuhong Wang 1,  Zhimeng Yao 1,  Kai Li 1,  Yichen Luo 1,  Fan Liu 1,  Yunlong Pan 5,  Sai-Ching J Yeung 6 7,  Wijnand Helfrich 2,  Hao Zhang 5 8
Affiliations

Affiliations

  • 1 Institute of Precision Cancer Medicine and Pathology, and Department of Pathology, School of Medicine, and Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, China.
  • 2 Department of Surgery, Laboratory for Translational Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • 3 Shantou University Medical College, Shantou, Guangdong, China.
  • 4 Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • 5 Department of General Surgery, The First Affiliated Hospital of Jinan University, and Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou, Guangdong, China.
  • 6 Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 7 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • 8 Minister of Education Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou, Guangdong, China.
PMID: 35927827 DOI: 10.1002/jev2.12243
Abstract

Cancer vaccines critically rely on the availability of targetable immunogenic cancer-specific neoepitopes. However, mutation-based immunogenic neoantigens are rare or even non-existent in subgroups of Cancer types. To address this issue, we exploited a cancer-specific aberrant transcription-induced chimeric RNA, designated A-Pas chiRNA, as a possible source of clinically relevant and targetable neoantigens. A-Pas chiRNA encodes a recently discovered cancer-specific chimeric protein that comprises full-length astrotactin-2 (ASTN2) C-terminally fused in-frame to the antisense sequence of the 18th intron of pregnancy-associated plasma protein-A (PAPPA). We used extracellular vesicles (EVs) from A-Pas chiRNA-transfected dendritic cells (DCs) to produce the cell-free Anticancer vaccine DEXA-P . Treatment of immunocompetent cancer-bearing mice with DEXA-P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer-specific transcription-induced chimeric RNAs can be exploited to produce a cell-free Cancer vaccine that induces potent CD8+ T cell-mediated Anticancer immunity. Our novel approach may be particularly useful for developing Cancer vaccines to treat malignancies with low mutational burden or without mutation-based antigens. Moreover, this cell-free Anticancer vaccine approach may offer several practical advantages over cell-based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life.

Keywords

EV-based cancer vaccine; mutation-independent neoantigen; transcription-induced chimeric RNA.

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