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Updated: Apr 24, 2026
Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Published on: January 6, 2014
Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system
Xin Xu1, Wael A H Hegazy2, Linjie Guo1
1Department of Pediatrics, Texas Children's Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
Abstract:
Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines.
Insights
This study introduces an oral Salmonella vaccine that effectively delivers tumor antigens to antigen-presenting cells, enhancing immune responses against cancer. The novel vaccine platform demonstrated significant antitumor activity and potential for therapeutic cancer vaccines.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Current cancer vaccines often use injectable vectors that may struggle to effectively present tumor-associated antigens (TAA).
- Oral vaccine delivery systems offer a novel approach to cancer immunotherapy.
- Salmonella-based vectors can be engineered to deliver antigens intracellularly.
Purpose of the Study:
- To develop and evaluate a novel orally administered Salmonella-based vaccine for cancer therapy.
- To optimize antigen delivery into antigen-presenting cells (APCs) using Salmonella Pathogenicity Island 2 (SPI2) effectors.
- To assess the immunogenicity and antitumor efficacy of the developed vaccine in preclinical cancer models.
Main Methods:
- Systematic screening of Salmonella SPI2 promoter:effector combinations for efficient TAA delivery.
- Engineering of an oral Salmonella vector expressing a codon-optimized survivin (coSVN) TAA.
- Evaluation of vaccine efficacy in CT26 colon carcinoma and A20 lymphoma mouse models.
- Assessment of immune cell infiltration, cytokine production (IL12, IFNγ), and tumor regression.
Main Results:
- A PsifB::sseJ::coSVN construct (p8032) showed maximal potency for antigen translocation and CD8 T cell presentation.
- Therapeutic vaccination with p8032 induced CXCR3-dependent CD8 T cell infiltration and reversed the CD8:Treg ratio in tumors.
- Combined treatment with p8032 and a natural killer T-cell ligand (7DW8-5) enhanced IL12 and IFNγ production, leading to complete tumor regression and memory formation.
Conclusions:
- An orally administered Salmonella vector system effectively delivers TAA into APCs, eliciting potent antitumor immune responses.
- The optimized Salmonella vector platform demonstrates significant potential for developing effective cancer vaccines.
- Combination therapy with immune-modulating agents can further enhance vaccine efficacy and induce durable antitumor memory.
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