alexa Enhancing the Anti-Tumor Effects of Cancer Peptide Vaccine Therapy | OMICS International
ISSN: 2157-7560
Journal of Vaccines & Vaccination

Like us on:

Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Enhancing the Anti-Tumor Effects of Cancer Peptide Vaccine Therapy

Norihiro Fujinami, Yu Sawada, Daisuke Nobuoka1 and Tetsuya Nakatsura*

Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan

*Corresponding Author:
Tetsuya Nakatsura
Division of Cancer Immunotherapy
Exploratory Oncology Research & Clinical Trial Center
National Cancer Center, Kashiwa, Chiba, Japan
Tel: +81-4-7131-5490
Fax: +81-4-7133-6606
E-mail: [email protected]

Received date: July 13, 2016; Accepted date: July 25, 2016; Published date: July 28, 2016

Citation: Fujinami N, Sawada Y, Nobuoka D, Nakatsura T (2016) Enhancing the Anti-Tumor Effects of Cancer Peptide Vaccine Therapy. J Vaccines Vaccin 7:330. doi: 10.4172/2157-7560.1000330

Copyright: © 2016 Fujinami N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Vaccines & Vaccination

Abstract

The clinical efficacy of cancer peptide vaccines has been considered inadequate. To enhance the anti-tumor effects of peptide vaccines, we have studied effective enhancement methods for peptide vaccine therapies such as intratumoral peptide injection and combination therapies with anti-PD-1 blocking antibody or anti-CD4 depletion antibody. We aim to present effective clinical applications of peptide vaccines.

Keywords

Peptide vaccine; Glypican-3; Intratumoral peptide injection; Anti-PD-1 blocking antibody; Anti-CD4 depletion antibody

Introduction

Cancer peptide vaccine therapies can be used to prolong survival while maintaining the quality of life (QOL) in patients and are expected to prevent or reduce recurrences. We have previously reported that glypican-3 (GPC3) is a cancer specific antigen [1-3] Studies have identified GPC3-derived peptides that are capable of inducing peptide-specific cytotoxic T lymphocytes (CTLs) [4-6]. Several clinical trials for the GPC3 peptide vaccine therapy have been performed in hepatocellular carcinoma (HCC) [7-9]. Through previous studies, we have confirmed the safety and immunological efficacy of the vaccine and demonstrated its potential in inducing clinical effects in some patients [8-10]. However, the clinical efficacy of cancer peptide vaccine therapies is still considered inadequate. Consequently, we have attempted to develop effective enhancement methods for peptide vaccine therapies.

Intratumoral peptide injection enhances tumor cell antigenicity

Antigen-specific cancer immunotherapy involves antigen-specific CTLs, which recognize the antigen-derived peptides bound to major histocompatibility complex (MHC) class I molecules on the tumor cell surface and destroy the tumor cells. The low density of presented antigen bound to MHC class I molecules is one of the reasons why antigen-specific cancer immunotherapy has been ineffective in a clinical setting. We confirmed that most of the tumors exhibited enhanced expression of the human leukocyte antigen (HLA) class I molecules and its expression within the tumor area was higher than that outside it. Therefore, to induce additional peptide loading onto MHC class I molecules present on the tumor cells, we performed the intratumoral peptide injection for effectively enhancing the anti-tumor effect of peptide vaccines.

Intratumoral peptide injection was effective in inhibiting tumor growth and prolonging survival time. Furthermore, an antigenspreading effect was detected after the peptide injection, which enhances tumor cell antigenicity and may be a valuable option in improving the anti-tumor effects of antigen-specific cancer immunotherapy against solid tumors [11].

Programmed death-1 (PD-1) blockade enhances the antitumor effects of peptide vaccines

PD-1 is expressed on activated T and B cells, and it induces inhibitory signals [12]. Several studies have shown that the PD-1/PDL1 pathway plays a critical role in compromised tumor immunity [13,14].

We have used peptide emulsified with incomplete Freundâ??s adjuvant (IFA) for peptide vaccines in both animal models and clinical models. However, the peptide/IFA vaccination increased antigen-driven expression of the inhibitory receptors PD-1, LAG-3, CTLA-4, and Tim-3 in CTLs [15]. PD-1 blockade could partially rescue CTLs in a state of exhaustion. Therefore we employed the combination therapy by using the peptide vaccine and PD-1 blocking antibody. We demonstrated that PD-1/PD-L1 blockade enhanced the anti-tumor effects of peptide vaccines by increasing the immune response of vaccine-induced CTLs [16].

Anti-tumor effects of peptide vaccines were enhanced in combination with anti-CD4 antibody

Several studies have suggested that the depletion of CD4+ cells results in strong anti-tumor effects in tumor-bearing mice models due to the enhancement of CTL responses [17-19].

To enhance the anti-tumor effects of peptide vaccines, we included an anti-CD4 monoclonal antibody (mAb) (clone: GK1.5) in a mouse model. Using the IFN--γ ELISPOT assay, we determined that the number of ovalbumin (OVA)-specific CTLs inducted by OVA peptide vaccine in combination with anti-CD4 mAb was higher than that inducted by OVA peptide vaccine alone. Additionally, after the combined treatment with OVA peptide vaccine and anti-CD4 mAb, perforin and granzyme secretion from CD107a+ cells increased and the production of IL-2 and TNF from these CTLs increased as analyzed by the CD107a assay and cytokine assay, respectively.

Finally, we observed that metastasis was remarkably suppressed by the peptide vaccine in combination with anti-CD4 mAb in a murine model of liver metastasis. The mouse model of liver metastasis was developed by injecting tumor cells into the spleen. The evaluation of liver metastasis was performed using the weight of the murine liver, because the number of metastases in the liver could not be counted too many. The liver weight of the combination group treated with the OVA peptide vaccine and anti-CD4 mAb was significantly lower than those of the untreated group and the group treated with OVA peptide vaccine alone. However, the liver weight of the combination group showed no significant difference from that of the group treated with anti-CD4 mAb alone [20]. However, we believe that the enhanced inhibitory effects on metastasis in the combination therapy was derived from the enhancement in the multi-functionality of peptidespecific CTLs as determined by the IFN-γ ELISPOT assay, CD107a upregulation assay and cytokine assay. Further investigations must be conducted to evaluate liver metastasis based on the number of liver metastases.

Conclusion

Although peptide vaccines exhibit disadvantages such as weak antitumor effects, they also have several advantages such as systemic effects similar to chemotherapies, with fewer side effects. Our therapeutic strategies such as intratumoral peptide injection or the combination therapies with antibody drugs can enhance the anti-tumor effect of cancer peptide vaccine therapy.

Acknowledgments

This study was supported in part by the National Cancer Center Research and Development Fund (25-A-7), and financial support from the Research on Applying Health Technology, the Research for Promotion of Cancer Control Programs, the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (AMED 15ck0106002h0103, 15ck0106109h0002).

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Article Usage

  • Total views: 8511
  • [From(publication date):
    August-2016 - May 22, 2018]
  • Breakdown by view type
  • HTML page views : 8403
  • PDF downloads : 108
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7