A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of antigen presenting cells

Young Seob Kim, Hyun Jin Park, Jung Hwa Park, Eun Ji Hong, Gun Young Jang, In Duk Jung, Hee Dong Han, Seung Hyun Lee, Manh Cuong Vo, Je Jung Lee, Andrew Yang, Emily Farmer, Tzyy Choou Wu, Tae Heung Kang, Yeong Min Park

Research output: Contribution to journalArticle

Abstract

Dendritic cell (DC)-based vaccines are recognized as a promising immunotherapeutic strategy against cancer. Various adjuvants are often incorporated to enhance the modest immunogenicity of DC vaccines. More specifically, many of the commonly used adjuvants are derived from bacteria. In the current study, we evaluate the use of apoptosis inhibitor 5 (API5), a damage-associated molecular pattern expressed by many human cancer cells, as a novel DC vaccine adjuvant. We showed that API5 can prompt activation and maturation of DCs and activate NFkB by stimulating the Toll-like receptor signaling pathway. We also demonstrated that vaccination with API5-treated DCs pulsed with OVA, E7, or AH1-A5 peptides led to the generation of OVA, E7, or AH1-A5-specific CD8 + T cells and memory T cells, which is associated with long term tumor protection and antitumor effects in mice, against EG.7, TC-1, and CT26 tumors. Additionally, we determined that API5-mediated DC activation and immune stimulation are dependent on TLR4. Lastly, we showed that the API5 protein sequence fragment that is proximal to its leucine zipper motif is responsible for the adjuvant effects exerted by API5. Our data provide evidence that support the use of API5 as a promising adjuvant for DC-based therapies, which can be applied in combination with other cancer therapies. Most notably, our results further support the continued investigation of human-based adjuvants.

Original languageEnglish (US)
JournalOncoImmunology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Antigen-Presenting Cells
Dendritic Cells
Apoptosis
Vaccines
Neoplasms
Inhibitor of Apoptosis Proteins
T-Lymphocytes
Leucine Zippers
Toll-Like Receptors
Cell- and Tissue-Based Therapy
Vaccination
Bacteria
Peptides

Keywords

  • adjuvants
  • API5
  • cancer vaccines
  • dendritic cells
  • TLR4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Kim, Y. S., Park, H. J., Park, J. H., Hong, E. J., Jang, G. Y., Jung, I. D., ... Park, Y. M. (Accepted/In press). A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of antigen presenting cells. OncoImmunology. https://doi.org/10.1080/2162402X.2018.1472187

A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of antigen presenting cells. / Kim, Young Seob; Park, Hyun Jin; Park, Jung Hwa; Hong, Eun Ji; Jang, Gun Young; Jung, In Duk; Han, Hee Dong; Lee, Seung Hyun; Vo, Manh Cuong; Lee, Je Jung; Yang, Andrew; Farmer, Emily; Wu, Tzyy Choou; Kang, Tae Heung; Park, Yeong Min.

In: OncoImmunology, 01.01.2018.

Research output: Contribution to journalArticle

Kim, YS, Park, HJ, Park, JH, Hong, EJ, Jang, GY, Jung, ID, Han, HD, Lee, SH, Vo, MC, Lee, JJ, Yang, A, Farmer, E, Wu, TC, Kang, TH & Park, YM 2018, 'A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of antigen presenting cells', OncoImmunology. https://doi.org/10.1080/2162402X.2018.1472187
Kim, Young Seob ; Park, Hyun Jin ; Park, Jung Hwa ; Hong, Eun Ji ; Jang, Gun Young ; Jung, In Duk ; Han, Hee Dong ; Lee, Seung Hyun ; Vo, Manh Cuong ; Lee, Je Jung ; Yang, Andrew ; Farmer, Emily ; Wu, Tzyy Choou ; Kang, Tae Heung ; Park, Yeong Min. / A novel function of API5 (apoptosis inhibitor 5), TLR4-dependent activation of antigen presenting cells. In: OncoImmunology. 2018.
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