A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy

Radford, Kristen J.; Higgins, Darren E.; Pasquini, Susanna; Cheadle, Eleanor J.; Carta, L; Jackson, Andrew M.; Lemoine, Nicholas R.; Vassaux, Georges

doi:10.1038/sj.gt.3301812

Cited by 63 publications

(82 citation statements)

References 31 publications

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“…Presentation required the presence of LLO, and antigen delivered by recombinant E. coli expressing MART1 but lacking LLO was not presented to MART1-specific CTLs. These findings are in agreement with our previous study using murine BMDCs, 19 where we showed that the presence of LLO in recombinant E. coli vaccines significantly enhanced the presentation of the OVA MHC class I peptide, SIINFEKL, and that this correlated with the degree of protection against challenge with syngeneic B16-OVA tumour.…”

Section: Discussionsupporting

confidence: 93%

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells

Radford

Jackson

Wang

et al. 2003

Intl Journal of Cancer

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The generation of tumour-specific cytotoxic T-lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. We have recently demonstrated generation of ovalbumin (OVA)-specific CTLs and tumour-protection in a murine tumour model using vaccination with dendritic cells (DCs) pulsed with E. coli expressing listeriolysin O (LLO) and OVA as a model antigen. In this system paraformaldehyde fixation of E. coli/LLO provided an additional safety feature without compromising vaccine efficacy. We therefore reasoned that paraformaldehyde-fixed recombinant E. coli expressing LLO would be an efficient vehicle for the delivery of human tumour antigens to human DCs. In the present study, we demonstrate that fixed E. coli expressing LLO are taken up efficiently by human monocytederived DCs (MoDCs) with minimal toxicity. As a consequence of the interaction with bacteria, human DCs undergo marked phenotypic and functional maturation. Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART1 27-35 epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy. © 2003 Wiley-Liss, Inc. Key words: dendritic cell; E. coli; tumour immunotherapyThe generation of tumour-specific cytotoxic T-lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. It is generally accepted that the initiation of effective antitumour immune responses relies upon antigen-presenting cells (APCs), most notably dendritic cells (DCs), priming CTLs and T helper cells, by processing antigen and presenting it on major histocompatibility (MHC) class I and class II molecules, respectively. DCs are unique in their potent ability to prime naïve T-cell responses, 1,2 and DCs loaded with tumour antigens show increasing potential as vaccine candidates in animal models 3,4 and early-phase clinical trials. [5][6][7][8][9] The generation of appropriate immune responses, and therefore successful vaccination, is highly dependent on the development of effective methods of antigen delivery to DCs. The ideal antigen delivery system should combine efficient processing and presentation of tumour antigens to CD8 ϩ T cells, along with potent DC activation in order to deliver the costimulatory signals necessary for T-cell priming. Preparations of tumour-specific antigens are desirable as less well defined whole tumour cell preparations or lysates contain selfantigens and may result in the induction autoimmunity. In addition, it is desirable to deliver the whole antigen to enable presentation of multiple epitopes without prior knowledge of the patient's HLA haplotype or the nature of the peptide epitopes.A number of vaccine strategies have already been shown to induce potent CTL responses, including infection with recombinant viruses, and DNA or RNA transfection. However, there are safety concerns with the expression of whole a...

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Section: Discussionsupporting

confidence: 93%

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells

Radford

Jackson

Wang

et al. 2003

Intl Journal of Cancer

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“…Recombinant E. coli have already been described as protein delivery vectors for professional phagocytic cells (ie macrophages, 26 in mouse DCs 27 and human monocyte-derived DCs). 28 E. coli coexpressing LLO and a model antigen (truncated chicken ovalbumin, OVA) were incubated with the cells, taken up and presentation of the OVA epitope on MHC class I was observed.…”

Section: Discussionmentioning

confidence: 99%

“…28 E. coli coexpressing LLO and a model antigen (truncated chicken ovalbumin, OVA) were incubated with the cells, taken up and presentation of the OVA epitope on MHC class I was observed. 26,27 In addition, an antitumour effect was observed when these bacteria were used in a vaccination protocol. 27 Similar in vitro data were obtained when human DCs were used to present MART-1 antigen epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 In addition, an antitumour effect was observed when these bacteria were used in a vaccination protocol. 27 Similar in vitro data were obtained when human DCs were used to present MART-1 antigen epitopes. 28 In the present communication, we have used an invasive E. coli to deliver therapeutically relevant molecules to mouse and human nonprofessional phagocytic cells.…”

Section: Discussionmentioning

confidence: 99%

“…But, at nontoxic doses, LLO increases the length of time during which a reporter protein is detectable (not shown) as well as in vitro therapeutic effect (Figure 4a). These effects are likely to be the result of the phagosomal pore-forming activity of LLO 13,16,17,26,27 that allows escape of the proteins expressed in bacteria into the cytosol (not shown) and therefore reduces their destruction in the lysosomal vesicle. …”

Section: Discussionmentioning

confidence: 99%

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Potential therapeutic applications of recombinant, invasive E. coli

et al. 2004

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Ovalbumin and Poly(i:c) Encapsulated Dendritic Cell‐Targeted Nanoparticles for Immune Activation in the Small Intestinal Lymphatic System

Kim

Lee

et al. 2022

Adv Healthcare Materials

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Here, antigen and adjuvant encapsulated dendritic cell-targeted nanoparticles for immune activation in the small intestinal lymphatic system to inhibit melanoma development are described. This strategy is demonstrated using chondroitin sulfate-coated nanoparticles (OPGMN) grafted with glycocholic acid and mannose for cationic liposomes encapsulated with ovalbumin as an antigen and polyinosine-polycytidylic acid as a cancer-specific adjuvant. OPGMN is absorbed in the gastrointestinal tract and delivered to the lymph nodes when orally administered. Oral delivery of OPGMN induces increased dendritic cell maturation compared to the intradermal route in the lymph node and induces T helper type 1 and type 2 responses, such as immunoglobulin G1 and G2c, interferon-gamma, and interleukin-2, in the blood. Repeated oral administration of OPGMN increases the population of CD3 + CD8 + T cells, CD44 high CD62L low memory T cells, and CD11b + CD27 + natural killer cells in the blood. OPGMN completely prevents melanoma development in the B16F10-bearing C57BL/6 mouse model by reducing the population of CD4 + CD25 + Foxp3 + regulatory T cells in the blood. This strategy is expected to prevent the recurrence of tumors after various cancer treatments.

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A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy

Cited by 63 publications

References 31 publications

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells

Potential therapeutic applications of recombinant, invasive E. coli

Ovalbumin and Poly(i:c) Encapsulated Dendritic Cell‐Targeted Nanoparticles for Immune Activation in the Small Intestinal Lymphatic System

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A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy

Cited by 63 publications

References 31 publications

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8+ T cells

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8+ T cells

Potential therapeutic applications of recombinant, invasive E. coli

Ovalbumin and Poly(i:c) Encapsulated Dendritic Cell‐Targeted Nanoparticles for Immune Activation in the Small Intestinal Lymphatic System

Contact Info

Product

Resources

About

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8⁺ T cells