Skip to main content

Advertisement

SpringerLink
Log in

Microbial HSP70 peptide epitope 407–426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Tumor-derived autophagome (DRibble) is an effective therapeutic cancer vaccine inducing T cell recognition and death of tumor cells in mice. However, the potential for improved anti-tumor response still remains. Our previous study demonstrated that two repeats of a mycobacterial HSP70407–426 (M2) peptide acted as adjuvant in improving anti-tumor efficacy of human umbilical vein endothelial cell (HUVEC) vaccine. Here, a DRibble vaccine conjugated with M2 (DRibble-M2) was designed as a novel vaccine to enhance anti-tumor activity. Compared with DRibble alone, DRibble-M2 vaccination more significantly inhibited the growth of mouse Lewis lung cancer both in a subcutaneous tumor model and in a lung metastasis model. Higher expression of antigen-specific CTL was induced by DRibble-M2. DRibble-M2 induced higher CD83 and CD86 expression in DC2.4 and also improved the internalization of DRibble antigen into DC2.4. Our data indicated that DRibble-M2 is a potential vaccine for clinical cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71. doi:10.3322/caac.21235.

    Article  PubMed  Google Scholar 

  2. Derman BA, Mileham KF, Bonomi PD, Batus M, Fidler MJ. Treatment of advanced squamous cell carcinoma of the lung: a review. Transl Lung Cancer Res. 2015;4(5):524–32. doi:10.3978/j.issn.2218-6751.2015.06.07.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Dzian A, Uhnak M, Hamzik J. Surgical treatment of lung metastases of colorectal carcinoma—survival and prognostic factors. Klin Onkol. 2015;28(5):345–51.

    Article  CAS  PubMed  Google Scholar 

  4. William Jr WN, Glisson BS. Novel strategies for the treatment of small-cell lung carcinoma. Nat Rev Clin Oncol. 2011;8(10):611–9. doi:10.1038/nrclinonc.2011.90.

    Article  CAS  PubMed  Google Scholar 

  5. Sawant A, Schafer CC, Jin TH, Zmijewski J, Tse HM, Roth J, et al. Enhancement of antitumor immunity in lung cancer by targeting myeloid-derived suppressor cell pathways. Cancer Res. 2013;73(22):6609–20. doi:10.1158/0008-5472.CAN-13-0987.

    Article  CAS  PubMed  Google Scholar 

  6. Mok TS, Loong HH. Are we ready for immune checkpoint inhibitors for advanced non-small-cell lung cancer? Lancet. 2016;387(10027):1488–90. doi:10.1016/S0140-6736(15)01308-2.

    Article  PubMed  Google Scholar 

  7. Tchekmedyian N, Gray JE, Creelan BC, Chiappori AA, Beg AA, Soliman H, et al. Propelling immunotherapy combinations into the clinic. Oncology (Williston Park). 2015;29(12).

  8. Anton LC, Yewdell JW. Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors. J Leukoc Biol. 2014;95(4):551–62. doi:10.1189/jlb.1113599.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yewdell JW. DRiPs solidify: progress in understanding endogenous MHC class I antigen processing. Trends Immunol. 2011;32(11):548–58. doi:10.1016/j.it.2011.08.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Twitty CG, Jensen SM, HM H, Fox BA. Tumor-derived autophagosome vaccine: induction of cross-protective immune responses against short-lived proteins through a p62-dependent mechanism. Clin Cancer Res. 2011;17(20):6467–81. doi:10.1158/1078-0432.CCR-11-0812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang Y, Whittall T, McGowan E, Younson J, Kelly C, Bergmeier LA, et al. Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells. J Immunol. 2005;174(6):3306–16.

    Article  CAS  PubMed  Google Scholar 

  12. Xu M, Zhou L, Zhang Y, Xie Z, Zhang J, Guo L, et al. A fixed human umbilical vein endothelial cell vaccine with 2 tandem repeats of microbial HSP70 peptide epitope 407-426 as adjuvant for therapy of hepatoma in mice. J Immunother. 2015;38(7):276–84. doi:10.1097/CJI.0000000000000091.

    Article  PubMed  Google Scholar 

  13. Li Y, Wang LX, Yang G, Hao F, Urba WJ, Efficient HHM. Cross-presentation depends on autophagy in tumor cells. Cancer Res. 2008;68(17):6889–95. doi:10.1158/0008-5472.CAN-08-0161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Welzel O, Loy K, Tischbirek CH, Tabor A, Gmeiner P, Kornhuber J, et al. The pH probe CypHer5E is effectively quenched by FM dyes. J Fluoresc. 2013;23(3):487–94. doi:10.1007/s10895-013-1164-3.

    Article  CAS  PubMed  Google Scholar 

  15. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342(6165):1432–3. doi:10.1126/science.342.6165.1432.

    Article  CAS  PubMed  Google Scholar 

  16. Coffin RS. Oncolytic immunotherapy: an emerging new modality for the treatment of cancer. Ann Oncol. 2016. doi:10.1093/annonc/mdw194.

    PubMed  Google Scholar 

  17. Smit EF, van den Heuvel MM. PD-L1 in non-small-cell lung cancer: the third target for immunotherapy. Lancet. 2016. doi:10.1016/S0140-6736(16)00700-5.

    PubMed Central  Google Scholar 

  18. Buhrman JD, Jordan KR, U’Ren L, Sprague J, Kemmler CB, Slansky JE. Augmenting antitumor T-cell responses to mimotope vaccination by boosting with native tumor antigens. Cancer Res. 2013;73(1):74–85. doi:10.1158/0008-5472.CAN-12-1005.

    Article  CAS  PubMed  Google Scholar 

  19. van Buuren MM, Calis JJ, Schumacher TN. High sensitivity of cancer exome-based CD8 T cell neo-antigen identification. Oncoimmunology. 2014;3:e28836. doi:10.4161/onci.28836.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Munz C. Of LAP, CUPS, and DRibbles—unconventional use of autophagy proteins for MHC restricted antigen presentation. Front Immunol. 2015;6:200. doi:10.3389/fimmu.2015.00200.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Li Y, Wang LX, Pang P, Twitty C, Fox BA, Aung S, et al. Cross-presentation of tumor associated antigens through tumor-derived autophagosomes. Autophagy. 2009;5(4):576–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ye W, Xing Y, Paustian C, van de Ven R, Moudgil T, Hilton TL, et al. Cross-presentation of viral antigens in dribbles leads to efficient activation of virus-specific human memory T cells. J Transl Med. 2014;12:100. doi:10.1186/1479-5876-12-100.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li H, Li Y, Jiao J, Alpha-alumina HHM. nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nat Nanotechnol. 2011;6(10):645–50. doi:10.1038/nnano.2011.153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lu Y, Ouyang K, Fang J, Zhang H, Wu G, Ma Y, et al. Improved efficacy of DNA vaccination against prostate carcinoma by boosting with recombinant protein vaccine and by introduction of a novel adjuvant epitope. Vaccine. 2009;27(39):5411–8. doi:10.1016/j.vaccine.2009.06.089.

    Article  CAS  PubMed  Google Scholar 

  25. Yi Y, Zhou Z, Shu S, Fang Y, Twitty C, Hilton TL, et al. Autophagy-assisted antigen cross-presentation: autophagosome as the argo of shared tumor-specific antigens and DAMPs. Oncoimmunology. 2012;1(6):976–8. doi:10.4161/onci.20059.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank Dr. Hong-Ming Hu for his contribution to this study. The study was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the National Natural Science Foundation of China (No. 81541158), the Promotive Research Fund for Young and Middle-Aged Scientists of Shandong Province (BS2014YY051), and the International Program of Nanjing Scientific and Technological Commission (201303049).

Author information

Authors and Affiliations

  1. Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, 210009, Nanjing, Jiangsu, People’s Republic of China

    Jian Li, Yun Xing, Wenjun Yao, Rongyue Cao, Taiming Li & Jie Wu

  2. Jinling Pharmaceutical Co., Ltd., 210009, Nanjing, Jiangsu, People’s Republic of China

    Jian Li

  3. Biotherapy Center of Nanjing Second Affiliated Hospital, Medical School, Southeast University, 210003, Nanjing, Jiangsu, People’s Republic of China

    Zhenxian Zhou

  4. School of Pharmacy, Binzhou Medical University, 264003, Yantai, Shandong, People’s Republic of China

    Maolei Xu

Authors
  1. Jian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenxian Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenjun Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rongyue Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Taiming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maolei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jie Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Maolei Xu or Jie Wu.

Ethics declarations

Conflicts of interest

None

Additional information

Jian Li and Yun Xing are contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Xing, Y., Zhou, Z. et al. Microbial HSP70 peptide epitope 407–426 as adjuvant in tumor-derived autophagosome vaccine therapy of mouse lung cancer. Tumor Biol. 37, 15097–15105 (2016). https://doi.org/10.1007/s13277-016-5309-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5309-2

Keywords

Search

Navigation