Immunotherapy with dendritic cells derived from bone marrow hematopoietic stems cells inhibited tumor growth on a TRAMP-C1 syngeneic mouse model of...

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Immunotherapy
Prostate Cancer
Presenter YUNLIM Kim
Citation Annals of Oncology (2018) 29 (suppl_9): ix67-ix73. 10.1093/annonc/mdy434
Authors Y. Kim1, B. Kim1, C. Kim1, H. Kim2, S.Y. Choi1, H. Lee2
  • 1Urology, Asan Medical Center, University of Ulsan College of Medicine, 138-931 - Seoul/KR
  • 2R&d, Pharmicell Co. Ltd, 13229 - Seongnam/KR

Abstract

Background

Worldwide, prostate cancer is the most prevalent cancer and a leading cause of cancer-related death among men. Within 5 years of initial diagnosis, approximately 10–20% of men will progress to metastatic castration-resistant prostate cancer (mCRPC). Despite the many options for the treatment of CRPC, including first- and second-line chemotherapy (docetaxel, cabazitaxel), anti-androgens (abiraterone, enzalutamide) and immunotherapy (sipuleucel-T), the clinical efficacy is limited. Dendritic cells (DCs) are the most potent antigen-presenting cells and are equipped with the necessary co-stimulatory, adhesion and histocompatibility molecules for initiation of a primary immune response. DC-based vaccination trials in solid cancers have aimed to activate the immune system to recognize and destroy tumor cells. In this study, we investigated the anticancer effect of prostate cancer using anti-cancer immunity cell vaccine based on the next generation dendritic cell immunotherapy.

Methods

Dendritic cells were injected once a week for three weeks into a TRAMP-C1 syngeneic mouse model and we investigated for safety, efficacy and induction of prostate cancer antigen-specific immune responses. And we also analyzed proliferation and activation of allogeneic-T cells by therapeutic dendritic cells. The effect of dendritic cells on survival of mice was analyzed by Kaplan-Meier methods.

Results

After DC treatment, tumor growth was significantly reduced in stem-DC compared to monocyte-drived dendritic cell (mono-DC) and vehicle group in TRAMP-C1 mouse model. In addition, stem-DC extended survival compared to the Mono-DC and vehicle treated group. To confirm stem-DC/tumor lysate induce more systemic anti-tumor immunity than Mo-DC/tumor lysate, we investigated effector T cells in splenic lymphocytes from mouse model. Finally, the frequency of IFN-γ secreting CD8+ T cells in stem-DC treated group was significantly higher than that in Mo-DC treated group.

Conclusions

Stem-DC, which was developed from hematopoietic stem cells in an optimized manner, proved to be effective and stable as an excellent anti-cancer immunotherapeutic agent for prostate cancer.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Asan Medical Center.

Funding

Korea Health Technology R&D Project, Ministry of Health & Welfare (Grant number: H16C2193).

Disclosure

All authors have declared no conflicts of interest.