A universal anti-cancer vaccine: Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival

Adi Sharbi-Yunger, Mareike Grees, Gal Cafri, David Bassan, Stefan B. Eichmüller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach

Research output: Contribution to journalArticle

Abstract

For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor-associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen. These DCs are then delivered to the host and elicit an immune response against the antigen of interest. We have recently established an mRNA genetic platform which induced specific CD8+ cytotoxic T cell response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs vaccine platform was developed to activate CD4+ T cells and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHC-II binding peptide sequences of melanoma antigens. These chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor specific CD4+ T cells. When administered in combination with the MHC-I platform into tumor bearing mice, these constructs were able to inhibit tumor growth, and improve mouse survival. Deciphering the immunological mechanism of action, we observed an efficient CTLs killing in addition to higher levels of Th1 and Th2 subsets in the groups immunized with a combination of the MHC-I and MHC-II constructs. These universal constructs can be applied in multiple combinations and offer an attractive opportunity to improve cancer treatment.

LanguageEnglish (US)
Pages909-921
Number of pages13
JournalInternational Journal of Cancer
Volume144
Issue number4
DOIs
StatePublished - Feb 15 2019

Fingerprint

Cancer Vaccines
Melanoma
T-Lymphocytes
Neoplasms
Neoplasm Antigens
Messenger RNA
Vaccination
Vaccines
Tumor Escape
Melanoma-Specific Antigens
Histocompatibility Antigens Class II
Immunotherapy
Transfection
invariant chain
Immune System
Growth

Keywords

  • chimeric construct
  • dendritic Cells
  • melanoma
  • MHC Class II
  • mRNA
  • vaccine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A universal anti-cancer vaccine : Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival. / Sharbi-Yunger, Adi; Grees, Mareike; Cafri, Gal; Bassan, David; Eichmüller, Stefan B.; Tzehoval, Esther; Utikal, Jochen; Umansky, Viktor; Eisenbach, Lea.

In: International Journal of Cancer, Vol. 144, No. 4, 15.02.2019, p. 909-921.

Research output: Contribution to journalArticle

Sharbi-Yunger, Adi ; Grees, Mareike ; Cafri, Gal ; Bassan, David ; Eichmüller, Stefan B. ; Tzehoval, Esther ; Utikal, Jochen ; Umansky, Viktor ; Eisenbach, Lea. / A universal anti-cancer vaccine : Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival. In: International Journal of Cancer. 2019 ; Vol. 144, No. 4. pp. 909-921.
@article{340d28119a0c4b31b91fd811a8f5d8ab,
title = "A universal anti-cancer vaccine: Chimeric invariant chain potentiates the inhibition of melanoma progression and the improvement of survival",
abstract = "For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor-associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen. These DCs are then delivered to the host and elicit an immune response against the antigen of interest. We have recently established an mRNA genetic platform which induced specific CD8+ cytotoxic T cell response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs vaccine platform was developed to activate CD4+ T cells and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHC-II binding peptide sequences of melanoma antigens. These chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor specific CD4+ T cells. When administered in combination with the MHC-I platform into tumor bearing mice, these constructs were able to inhibit tumor growth, and improve mouse survival. Deciphering the immunological mechanism of action, we observed an efficient CTLs killing in addition to higher levels of Th1 and Th2 subsets in the groups immunized with a combination of the MHC-I and MHC-II constructs. These universal constructs can be applied in multiple combinations and offer an attractive opportunity to improve cancer treatment.",
keywords = "chimeric construct, dendritic Cells, melanoma, MHC Class II, mRNA, vaccine",
author = "Adi Sharbi-Yunger and Mareike Grees and Gal Cafri and David Bassan and Eichm{\"u}ller, {Stefan B.} and Esther Tzehoval and Jochen Utikal and Viktor Umansky and Lea Eisenbach",
year = "2019",
month = "2",
day = "15",
doi = "10.1002/ijc.31795",
language = "English (US)",
volume = "144",
pages = "909--921",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - A universal anti-cancer vaccine

T2 - International Journal of Cancer

AU - Sharbi-Yunger, Adi

AU - Grees, Mareike

AU - Cafri, Gal

AU - Bassan, David

AU - Eichmüller, Stefan B.

AU - Tzehoval, Esther

AU - Utikal, Jochen

AU - Umansky, Viktor

AU - Eisenbach, Lea

PY - 2019/2/15

Y1 - 2019/2/15

N2 - For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor-associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen. These DCs are then delivered to the host and elicit an immune response against the antigen of interest. We have recently established an mRNA genetic platform which induced specific CD8+ cytotoxic T cell response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs vaccine platform was developed to activate CD4+ T cells and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHC-II binding peptide sequences of melanoma antigens. These chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor specific CD4+ T cells. When administered in combination with the MHC-I platform into tumor bearing mice, these constructs were able to inhibit tumor growth, and improve mouse survival. Deciphering the immunological mechanism of action, we observed an efficient CTLs killing in addition to higher levels of Th1 and Th2 subsets in the groups immunized with a combination of the MHC-I and MHC-II constructs. These universal constructs can be applied in multiple combinations and offer an attractive opportunity to improve cancer treatment.

AB - For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor-associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen. These DCs are then delivered to the host and elicit an immune response against the antigen of interest. We have recently established an mRNA genetic platform which induced specific CD8+ cytotoxic T cell response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs vaccine platform was developed to activate CD4+ T cells and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHC-II binding peptide sequences of melanoma antigens. These chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor specific CD4+ T cells. When administered in combination with the MHC-I platform into tumor bearing mice, these constructs were able to inhibit tumor growth, and improve mouse survival. Deciphering the immunological mechanism of action, we observed an efficient CTLs killing in addition to higher levels of Th1 and Th2 subsets in the groups immunized with a combination of the MHC-I and MHC-II constructs. These universal constructs can be applied in multiple combinations and offer an attractive opportunity to improve cancer treatment.

KW - chimeric construct

KW - dendritic Cells

KW - melanoma

KW - MHC Class II

KW - mRNA

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85058059061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058059061&partnerID=8YFLogxK

U2 - 10.1002/ijc.31795

DO - 10.1002/ijc.31795

M3 - Article

VL - 144

SP - 909

EP - 921

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -