Abstract
A major challenge for developing effective therapeutic vaccines against cancer is overcoming immunologic tolerance to tumor-associated antigens that are expressed on both malignant cells and normal tissues. Herein, we describe a novel vaccination approach, TriVax, that uses synthetic peptides representing CD8 T-cell epitopes, Toll-like receptor agonists that function as potent immunologic adjuvants and costimulatory anti-CD40 antibodies to generate large numbers of high-avidity antigen-reactive T cells capable of recognizing and killing tumor cells. Our results show that TriVax induced huge numbers of long-lasting antigen-specific CD8 T cells that displayed significant antitumor effects in vivo. The administration of a TriVax formulation containing a CD8 T-cell epitope derived from a melanosomal antigen (Trp2180-188) elicited antigen-specific CD8 T cells that induced systemic autoimmunity (vitiligo). More important, TriVax immunization was effective in eliciting potent protective antitumor immunity as well as remarkable therapeutic effects against established B16 melanoma. This therapeutic effect was mediated by CD8 T cells via perforin-mediated lysis and required the participation of type-I IFN but not IFNγ. These results suggest that similar strategies would be applicable for the design of effective vaccination for conducting clinical studies in cancer patients.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9012-9019 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 69 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 1 2009 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. / Cho, Hyun Il; Celis, Esteban.
In: Cancer Research, Vol. 69, No. 23, 01.12.2009, p. 9012-9019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects
AU - Cho, Hyun Il
AU - Celis, Esteban
PY - 2009/12/1
Y1 - 2009/12/1
N2 - A major challenge for developing effective therapeutic vaccines against cancer is overcoming immunologic tolerance to tumor-associated antigens that are expressed on both malignant cells and normal tissues. Herein, we describe a novel vaccination approach, TriVax, that uses synthetic peptides representing CD8 T-cell epitopes, Toll-like receptor agonists that function as potent immunologic adjuvants and costimulatory anti-CD40 antibodies to generate large numbers of high-avidity antigen-reactive T cells capable of recognizing and killing tumor cells. Our results show that TriVax induced huge numbers of long-lasting antigen-specific CD8 T cells that displayed significant antitumor effects in vivo. The administration of a TriVax formulation containing a CD8 T-cell epitope derived from a melanosomal antigen (Trp2180-188) elicited antigen-specific CD8 T cells that induced systemic autoimmunity (vitiligo). More important, TriVax immunization was effective in eliciting potent protective antitumor immunity as well as remarkable therapeutic effects against established B16 melanoma. This therapeutic effect was mediated by CD8 T cells via perforin-mediated lysis and required the participation of type-I IFN but not IFNγ. These results suggest that similar strategies would be applicable for the design of effective vaccination for conducting clinical studies in cancer patients.
AB - A major challenge for developing effective therapeutic vaccines against cancer is overcoming immunologic tolerance to tumor-associated antigens that are expressed on both malignant cells and normal tissues. Herein, we describe a novel vaccination approach, TriVax, that uses synthetic peptides representing CD8 T-cell epitopes, Toll-like receptor agonists that function as potent immunologic adjuvants and costimulatory anti-CD40 antibodies to generate large numbers of high-avidity antigen-reactive T cells capable of recognizing and killing tumor cells. Our results show that TriVax induced huge numbers of long-lasting antigen-specific CD8 T cells that displayed significant antitumor effects in vivo. The administration of a TriVax formulation containing a CD8 T-cell epitope derived from a melanosomal antigen (Trp2180-188) elicited antigen-specific CD8 T cells that induced systemic autoimmunity (vitiligo). More important, TriVax immunization was effective in eliciting potent protective antitumor immunity as well as remarkable therapeutic effects against established B16 melanoma. This therapeutic effect was mediated by CD8 T cells via perforin-mediated lysis and required the participation of type-I IFN but not IFNγ. These results suggest that similar strategies would be applicable for the design of effective vaccination for conducting clinical studies in cancer patients.
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U2 - 10.1158/0008-5472.CAN-09-2019
DO - 10.1158/0008-5472.CAN-09-2019
M3 - Article
C2 - 19903852
AN - SCOPUS:71549172516
VL - 69
SP - 9012
EP - 9019
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 23
ER -