CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells

Antoni Ribas, Lisa H. Butterfield, Saral N. Amarnani, Vivian B. Dissette, Donald Kim, Wilson S. Meng, Gustavo Miranda-Carboni, James S. Economou, Antoni Ribas, John A. Glaspy, He Jing Wang, William H. McBride, James S. Economou

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knockout (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type C57BL/6 mice revealed an overall enhancement of antitumor immunity. However, this effect was inconsistent between replicate studies. In conclusion, maturation of AdVMART1-transduced DCs through the CD40 ligation pathway can promote a protective CD8 T-cell-mediated immunity that is independent of CD4 T-cell help.

Original languageEnglish (US)
Pages (from-to)8787-8793
Number of pages7
JournalCancer Research
Volume61
Issue number24
StatePublished - Dec 15 2001

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Melanoma-Specific Antigens
Dendritic Cells
Immunization
T-Lymphocytes
Genes
Ligation
Interleukin-7
Interleukin-12
Inbred C57BL Mouse
Knockout Mice
Cellular Immunity
Immunotherapy
Interleukin-2
Immunity
Melanoma
Animal Models
Cytokines
Antigens
Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ribas, A., Butterfield, L. H., Amarnani, S. N., Dissette, V. B., Kim, D., Meng, W. S., ... Economou, J. S. (2001). CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells. Cancer Research, 61(24), 8787-8793.

CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells. / Ribas, Antoni; Butterfield, Lisa H.; Amarnani, Saral N.; Dissette, Vivian B.; Kim, Donald; Meng, Wilson S.; Miranda-Carboni, Gustavo; Economou, James S.; Ribas, Antoni; Glaspy, John A.; Wang, He Jing; McBride, William H.; Economou, James S.

In: Cancer Research, Vol. 61, No. 24, 15.12.2001, p. 8787-8793.

Research output: Contribution to journalArticle

Ribas, A, Butterfield, LH, Amarnani, SN, Dissette, VB, Kim, D, Meng, WS, Miranda-Carboni, G, Economou, JS, Ribas, A, Glaspy, JA, Wang, HJ, McBride, WH & Economou, JS 2001, 'CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells', Cancer Research, vol. 61, no. 24, pp. 8787-8793.
Ribas A, Butterfield LH, Amarnani SN, Dissette VB, Kim D, Meng WS et al. CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells. Cancer Research. 2001 Dec 15;61(24):8787-8793.
Ribas, Antoni ; Butterfield, Lisa H. ; Amarnani, Saral N. ; Dissette, Vivian B. ; Kim, Donald ; Meng, Wilson S. ; Miranda-Carboni, Gustavo ; Economou, James S. ; Ribas, Antoni ; Glaspy, John A. ; Wang, He Jing ; McBride, William H. ; Economou, James S. / CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells. In: Cancer Research. 2001 ; Vol. 61, No. 24. pp. 8787-8793.
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abstract = "Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knockout (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type C57BL/6 mice revealed an overall enhancement of antitumor immunity. However, this effect was inconsistent between replicate studies. In conclusion, maturation of AdVMART1-transduced DCs through the CD40 ligation pathway can promote a protective CD8 T-cell-mediated immunity that is independent of CD4 T-cell help.",
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