Combination Immunotherapy with 4-1BBL and CTLA-4 Blockade for the Treatment of Prostate Cancer
Open Access
- 1 January 2012
- journal article
- research article
- Published by Hindawi Limited in Journal of Immunology Research
- Vol. 2012, 1-6
- https://doi.org/10.1155/2012/439235
Abstract
Immune regulation has been shown to be involved in the progressive growth of some murine tumours. Interruption of immune regulatory pathways via activation of 4-1BB or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade appears to be a promising strategy for cancer immunotherapy. In this study, we examined the effectiveness of 4-1BBL-expressing tumor cell vaccine in combination with CTLA-4 blockade on rejection of murine prostate cancer RM-1. We found that the combination of both a vaccine consisting of 4-1BBL-expressing RM-1 cells and CTLA-4 blockade resulted in regression of RM-1 tumors and a significant increase in survival of the tumour cell recipients, compared to that of either treatment alone. The combined vaccination resulted in higher CTL against RM-1 cells and increased secretion of IFN-, TNF- and IL-2 in the mix-cultured supernatant. These results suggest that combining activation of 4-1BB and blockade of CTLA-4 may offer a new strategy for prostate cancer immunotherapy.Keywords
Funding Information
- National Natural Science Foundation of China (30672107)
This publication has 29 references indexed in Scilit:
- The effect of a therapeutic dendritic cell-based cancer vaccination depends on the blockage of CTLA-4 signalingCancer Letters, 2006
- Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivoBlood, 2004
- Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?Nature Reviews Immunology, 2003
- 4-1BB Promotes the Survival of CD8+ T Lymphocytes by Increasing Expression of Bcl-xL and Bfl-1The Journal of Immunology, 2002
- Signaling Through NK Cell-Associated CD137 Promotes Both Helper Function for CD8+ Cytolytic T Cells and Responsiveness to IL-2 But Not Cytolytic ActivityThe Journal of Immunology, 2002
- 4-1BB co-stimulation enhances human CD8+ T cell priming by augmenting the proliferation and survival of effector CD8+ T cellsInternational Immunology, 2002
- 4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar EfficacyThe Journal of Immunology, 2001
- 4-1BBL Enhances Anti-tumor Responses in the Presence or Absence of CD28 but CD28 Is Required for Protective Immunity against Parental TumorsCellular Immunology, 2001
- In vivoblockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific toleranceProceedings of the National Academy of Sciences of the United States of America, 1999
- Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune DepigmentationThe Journal of Experimental Medicine, 1999