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Article ; Online: Cancer immunotherapy using recombinant Listeria monocytogenes: transition from bench to clinic.

Singh, Reshma / Wallecha, Anu

Human vaccines

2011 Volume 7, Issue 5, Page(s) 497–505

Abstract: Cancer immunotherapy has developed into a field of intense study as aspects of the immune system involved in the eradication of cancer have become delineated. Listeria monocytogenes is a gram-positive, facultative intracellular bacterium which infects ... ...

Abstract	Cancer immunotherapy has developed into a field of intense study as aspects of the immune system involved in the eradication of cancer have become delineated. Listeria monocytogenes is a gram-positive, facultative intracellular bacterium which infects antigen presenting cells (APC), and is being used as a cancer vaccine to deliver tumor antigens directly to the APC. This results in the generation of a strong immune response towards the tumor associated antigen and direct targeting of the tumor by the immune system. Advances in this field have led to the development of a series of L. monocytogenes-based cancer vaccines, which are currently in clinical trials. A phase I study has shown these vaccines can be safely administered and well-tolerated in terminal stage cancer patients and an efficacy signal was observed in patients who did not respond to other therapies. Additional data on the efficacy of these vaccines is expected in the near-term.
MeSH term(s)	Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Clinical Trials as Topic ; Humans ; Immunotherapy/methods ; Listeria monocytogenes/genetics ; Listeria monocytogenes/immunology ; Neoplasms/therapy ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology
Chemical Substances	Antigens, Neoplasm ; Cancer Vaccines ; Vaccines, Synthetic
Language	English
Publishing date	2011-05-01
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1554-8619
ISSN (online)	1554-8619
DOI	10.4161/hv.7.5.15132
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment.

Wallecha, Anu / Singh, Reshma / Malinina, Inga

Journal of immunotherapy (Hagerstown, Md. : 1997)

2013 Volume 36, Issue 9, Page(s) 468–476

Abstract: Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown ... ...

Abstract	Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. The results presented here provide insight into a novel mechanism of Lm-LLO immunotherapies that potentially contributes to therapeutic antitumor responses.
MeSH term(s)	Animals ; Arginase/genetics ; Arginase/immunology ; Arginase/metabolism ; Bacterial Toxins/immunology ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Cell Line, Tumor ; Female ; Flow Cytometry ; Gene Expression/immunology ; Heat-Shock Proteins/immunology ; Hemolysin Proteins/immunology ; Immune Tolerance/immunology ; Immunotherapy/methods ; Interleukin-10/genetics ; Interleukin-10/immunology ; Interleukin-10/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/therapy ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
Chemical Substances	Bacterial Toxins ; Cancer Vaccines ; Heat-Shock Proteins ; Hemolysin Proteins ; Interleukin-10 (130068-27-8) ; Arg1 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1) ; hlyA protein, Listeria monocytogenes (R06ZRQ1YX9)
Language	English
Publishing date	2013-10-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000000
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Article ; Online: Listeria monocytogenes: a promising vehicle for neonatal vaccination.

Liang, Zach Z / Sherrid, Ashley M / Wallecha, Anu / Kollmann, Tobias R

Human vaccines & immunotherapeutics

2014 Volume 10, Issue 4, Page(s) 1036–1046

Abstract: Vaccination as a medical intervention has proven capable of greatly reducing the suffering from childhood infectious disease. However, newborns and infants in particular are age groups for whom adequate vaccine-mediated protection is still largely ... ...

Abstract	Vaccination as a medical intervention has proven capable of greatly reducing the suffering from childhood infectious disease. However, newborns and infants in particular are age groups for whom adequate vaccine-mediated protection is still largely lacking. With the challenges that the neonatal immune system faces and the required highest level of stringency for safety, designing vaccines for early life in general and the newborn in particular poses great difficulty. Nevertheless, recent advances in our understanding of neonatal immunity and its responses to vaccines and adjuvants suggest that neonatal vaccination is a task fully within reach. Among the most promising developments in neonatal vaccination is the use of Listeria monocytogenes (Lm) as a delivery platform. In this review, we will outline key properties of Lm that make it such an ideal neonatal and early life vaccine vehicle, and also discuss potential constraints of Lm as a vaccine delivery platform.
MeSH term(s)	Drug Carriers ; Genetic Vectors ; Humans ; Listeria monocytogenes/genetics ; Vaccination/methods ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology
Chemical Substances	Drug Carriers ; Vaccines, Synthetic
Language	English
Publishing date	2014-02-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.4161/hv.27999
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Article: Control of Gene Expression at a Bacterial Leader RNA, the agn43 Gene Encoding Outer Membrane Protein Ag43 of Escherichia coli

Wallecha, Anu / Oreh, Heather / van der Woude, Marjan W / deHaseth, Pieter L

Journal of bacteriology. 2014 Aug. 1, v. 196, no. 15

2014

Abstract: The family of agn alleles in Escherichia coli pathovars encodes autotransporters that have been implicated in biofilm formation, autoaggregation, and attachment to cells. The alleles all have long leader RNAs preceding the Ag43 translation initiation ... ...

Abstract	The family of agn alleles in Escherichia coli pathovars encodes autotransporters that have been implicated in biofilm formation, autoaggregation, and attachment to cells. The alleles all have long leader RNAs preceding the Ag43 translation initiation codon. Here we present an analysis of the agn43 leader RNA from E. coli K-12. We demonstrate the presence of a rho-independent transcription terminator just 28 bp upstream of the main translation start codon and show that it is functional in vitro. Our data indicate that an as-yet-unknown mechanism of antitermination of transcription must be operative in earlier phases of growth. However, as bacterial cell cultures mature, progressively fewer transcripts are able to bypass this terminator. In the K-12 leader sequence, two in-frame translation initiation codons have been identified, one upstream and the other downstream of the transcription terminator. For optimal agn43 expression, both codons need to be present. Translation from the upstream start codon leads to increased downstream agn43 expression. Our findings have revealed two novel modes of regulation of agn43 expression in the leader RNA in addition to the previously well-characterized regulation of phase variation at the agn43 promoter.
Keywords	Escherichia coli ; RNA ; alleles ; bacteria ; bacteriology ; biofilm ; cell culture ; gene expression ; outer membrane proteins ; pathovars ; start codon ; translation (genetics)
Language	English
Dates of publication	2014-0801
Size	p. 2728-2735.
Publishing place	American Society for Microbiology
Document type	Article
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.01680-14
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Article ; Online: Episomal expression of truncated listeriolysin O in LmddA-LLO-E7 vaccine enhances antitumor efficacy by preferentially inducing expansions of CD4+FoxP3- and CD8+ T cells.

Chen, Zhisong / Ozbun, Laurent / Chong, Namju / Wallecha, Anu / Berzofsky, Jay A / Khleif, Samir N

Cancer immunology research

2014 Volume 2, Issue 9, Page(s) 911–922

Abstract: Studies have shown that Listeria monocytogenes (Lm)-based vaccine expressing a fusion protein comprising truncated listeriolysin O (LLO) and human papilloma virus (HPV) E7 protein (Lm-LLO-E7) induces a decrease in regulatory T cells (Treg) and complete ... ...

Abstract	Studies have shown that Listeria monocytogenes (Lm)-based vaccine expressing a fusion protein comprising truncated listeriolysin O (LLO) and human papilloma virus (HPV) E7 protein (Lm-LLO-E7) induces a decrease in regulatory T cells (Treg) and complete regression of established, transplanted HPV-TC-1 tumors in mice. However, how the Lm-based vaccine causes a decrease in Tregs remains unclear. Using a highly attenuated Lm dal dat ΔactA strain (LmddA)-based vaccine, we report here that the vector LmddA was sufficient to induce a decrease in the proportion of Tregs by preferentially expanding CD4(+)FoxP3(-) T cells and CD8(+) T cells by a mechanism dependent on and directly mediated by LLO. Episomal expression of a nonhemolytic truncated LLO in Lm (LmddA-LLO) significantly augmented the expansion, thus further decreasing Treg frequency. Although adoptive transfer of Tregs compromised the antitumor efficacy of the LmddA-LLO-E7 vaccine, a combination of LmddA-LLO and an Lm-based vaccine expressing E7 protein (Lm-E7) induced complete regression against established TC-1 tumors. An engineered LLO-minus Lm expressing perfringolysin O (PFO) that enables the recombinant bacteria to exit from the phagolysosome without LLO confirmed that the adjuvant effect was dependent on LLO. These results suggest that LLO may serve as a promising adjuvant by preferentially inducing the expansions of CD4(+)FoxP3(-) T cells and CD8(+) T cells, thus reducing the ratio of Tregs to CD4(+)FoxP3(-) T cells and to CD8(+) T cells favoring immune responses to eradicate tumor.
MeSH term(s)	Adoptive Transfer ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Cancer Vaccines/therapeutic use ; Cell Line, Tumor ; Female ; Genetic Vectors ; Listeria monocytogenes/genetics ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/therapy ; Papillomavirus E7 Proteins/genetics ; Plasmids/genetics ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Cancer Vaccines ; Papillomavirus E7 Proteins
Language	English
Publishing date	2014-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-13-0197
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Article ; Online: Control of gene expression at a bacterial leader RNA, the agn43 gene encoding outer membrane protein Ag43 of Escherichia coli.

Wallecha, Anu / Oreh, Heather / van der Woude, Marjan W / deHaseth, Pieter L

Journal of bacteriology

2014 Volume 196, Issue 15, Page(s) 2728–2735

Abstract	The family of agn alleles in Escherichia coli pathovars encodes autotransporters that have been implicated in biofilm formation, autoaggregation, and attachment to cells. The alleles all have long leader RNAs preceding the Ag43 translation initiation codon. Here we present an analysis of the agn43 leader RNA from E. coli K-12. We demonstrate the presence of a rho-independent transcription terminator just 28 bp upstream of the main translation start codon and show that it is functional in vitro. Our data indicate that an as-yet-unknown mechanism of antitermination of transcription must be operative in earlier phases of growth. However, as bacterial cell cultures mature, progressively fewer transcripts are able to bypass this terminator. In the K-12 leader sequence, two in-frame translation initiation codons have been identified, one upstream and the other downstream of the transcription terminator. For optimal agn43 expression, both codons need to be present. Translation from the upstream start codon leads to increased downstream agn43 expression. Our findings have revealed two novel modes of regulation of agn43 expression in the leader RNA in addition to the previously well-characterized regulation of phase variation at the agn43 promoter.
MeSH term(s)	5' Untranslated Regions/genetics ; Adhesins, Escherichia coli/genetics ; Bacterial Outer Membrane Proteins/genetics ; Escherichia coli K12/genetics ; Gene Expression Regulation, Bacterial/genetics ; Genes, Reporter ; Promoter Regions, Genetic/genetics ; RNA Stability ; RNA, Bacterial/genetics ; RNA, Messenger/genetics ; Terminator Regions, Genetic/genetics ; Transcription, Genetic
Chemical Substances	5' Untranslated Regions ; Adhesins, Escherichia coli ; Bacterial Outer Membrane Proteins ; RNA, Bacterial ; RNA, Messenger ; antigen 43, E coli
Language	English
Publishing date	2014-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.01680-14
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Article: Purification and characterization of two beta-glucosidases from a thermo-tolerant yeast Pichia etchellsii.

Wallecha, Anu / Mishra, Saroj

Biochimica et biophysica acta

2003 Volume 1649, Issue 1, Page(s) 74–84

Abstract: The thermo-tolerant yeast Pichia etchellsii produced two cell-wall-bound inducible beta-glucosidases, BGLI (molecular mass 186 kDa) and BGLII (molecular mass 340 kDa), which were purified by a simple, three-step method, comprising ammonium sulfate ... ...

Abstract	The thermo-tolerant yeast Pichia etchellsii produced two cell-wall-bound inducible beta-glucosidases, BGLI (molecular mass 186 kDa) and BGLII (molecular mass 340 kDa), which were purified by a simple, three-step method, comprising ammonium sulfate precipitation, ion-exchange and hydroxyapatite chromatography. The two enzymes exhibited a similar pH and temperature optima, inhibitory effect by glucose and gluconolactone, and stability in the pH range of 3.0-9.0. Placed in family 3 of glycosylhydrolase families, BGLI was more active on salicin, p-nitrophenyl beta-D-glucopyranoside and alkyl beta-D-glucosides whereas BGLII was most active on cellobiose. k(cat) and K(M) values were determined for a number of substrates and, for BGLI, it was established that the deglycosylation step was equally effective on aryl- and alkyl-glucosides while the glycosylation step varied depending on the substrate used. This information was used to synthesize alkyl-glucosides (up to a chain length of C(10)) using dimethyl sulfoxide stabilized single-phase reaction microenvironment. About 12% molar yield of octyl-glucoside was calculated based on a simple spectrophotometric method developed for its estimation. Further, detailed comparison of properties of the enzymes indicated these to be different from the previously cloned beta-glucosidases from this yeast.
MeSH term(s)	Amino Acids/analysis ; Benzyl Alcohols/metabolism ; Cellobiose/metabolism ; Cloning, Molecular ; Enzyme Activation/drug effects ; Fungal Proteins/chemistry ; Fungal Proteins/drug effects ; Fungal Proteins/genetics ; Fungal Proteins/isolation & purification ; Gluconates/metabolism ; Gluconates/pharmacology ; Glucose/metabolism ; Glucose/pharmacology ; Glucosides ; Glycosylation ; Hydrogen-Ion Concentration ; Lactones ; Metals/pharmacology ; Molecular Weight ; Pichia/enzymology ; Pichia/genetics ; Sequence Analysis, Protein ; Solvents/pharmacology ; Substrate Specificity ; Temperature ; beta-Glucosidase/chemistry ; beta-Glucosidase/drug effects ; beta-Glucosidase/genetics ; beta-Glucosidase/isolation & purification
Chemical Substances	Amino Acids ; Benzyl Alcohols ; Fungal Proteins ; Gluconates ; Glucosides ; Lactones ; Metals ; Solvents ; Cellobiose (16462-44-5) ; salicin (4649620TBZ) ; beta-Glucosidase (EC 3.2.1.21) ; Glucose (IY9XDZ35W2) ; beta-glucono-1,5-lactone (WQ29KQ9POT)
Language	English
Publishing date	2003-06-11
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/s1570-9639(03)00163-8
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Article ; Online: Live, attenuated strains of Listeria and Salmonella as vaccine vectors in cancer treatment.

Shahabi, Vafa / Maciag, Paulo C / Rivera, Sandra / Wallecha, Anu

Bioengineered bugs

2010 Volume 1, Issue 4, Page(s) 235–243

Abstract: Live, attenuated strains of many bacteria that synthesize and secrete foreign antigens are being developed as vaccines for a number of infectious diseases and cancer. Bacterial-based vaccines provide a number of advantages over other antigen delivery ... ...

Abstract	Live, attenuated strains of many bacteria that synthesize and secrete foreign antigens are being developed as vaccines for a number of infectious diseases and cancer. Bacterial-based vaccines provide a number of advantages over other antigen delivery strategies including low cost of production, the absence of animal products, genetic stability and safety. In addition, bacterial vaccines delivering a tumor-associated antigen (TAA) stimulate innate immunity and also activate both arms of the adaptive immune system by which they exert efficacious anti-tumor effects. Listeria monocytogenes and several strains of Salmonella have been most extensively studied for this purpose. A number of attenuated strains have been generated and used to deliver antigens associated with infectious diseases and cancer. Although both bacteria are intracellular, the immune responses invoked by Listeria and Salmonella are different due to their sub-cellular locations. Upon entering antigen-presenting cells by phagocytosis, Listeria is capable of escaping from the phagosomal compartment and thus has direct access to the cell cytosol. Proteins delivered by this vector behave as endogenous antigens, are presented on the cell surface in the context of MHC class I molecules, and generate strong cell-mediated immune responses. In contrast, proteins delivered by Salmonella, which lacks a phagosomal escape mechanism, are treated as exogenous antigens and presented by MHC class II molecules resulting predominantly in Th2 type immune responses. This fundamental disparity between the life cycles of the two vectors accounts for their differential application as antigen delivery vehicles. The present paper includes a review of the most recent advances in the development of these two bacterial vectors for treatment of cancer. Similarities and differences between the two vectors are discussed.
MeSH term(s)	Animals ; Antigen-Presenting Cells/immunology ; Cancer Vaccines/immunology ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Humans ; Listeria/immunology ; Listeria/metabolism ; Models, Biological ; Neoplasms/immunology ; Salmonella/immunology ; Salmonella/metabolism
Chemical Substances	Cancer Vaccines ; Histocompatibility Antigens Class I
Language	English
Publishing date	2010-01-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2623145-1
ISSN	1949-1026 ; 1949-1018
ISSN (online)	1949-1026
ISSN	1949-1018
DOI	10.4161/bbug.1.4.11243
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Article ; Online: Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular pattern-like properties independent of its hemolytic ability.

Wallecha, Anu / Wood, Laurence / Pan, Zhen-Kun / Maciag, Paulo C / Shahabi, Vafa / Paterson, Yvonne

Clinical and vaccine immunology : CVI

2012 Volume 20, Issue 1, Page(s) 77–84

Abstract: There is a constant need for improved adjuvants to augment the induction of immune responses against tumor-associated antigens (TAA) during immunotherapy. Previous studies have established that listeriolysin O (LLO), a cholesterol-dependent cytolysin ... ...

Abstract	There is a constant need for improved adjuvants to augment the induction of immune responses against tumor-associated antigens (TAA) during immunotherapy. Previous studies have established that listeriolysin O (LLO), a cholesterol-dependent cytolysin derived from Listeria monocytogenes, exhibits multifaceted effects to boost the stimulation of immune responses to a variety of antigens. However, the direct ability of LLO as an adjuvant and whether it acts as a pathogen-associated molecular pattern (PAMP) have not been demonstrated. In this paper, we show that a detoxified, nonhemolytic form of LLO (dtLLO) is an effective adjuvant in tumor immunotherapy and may activate innate and cellular immune responses by acting as a PAMP. Our investigation of the adjuvant activity demonstrates that dtLLO, either fused to or administered as a mixture with a human papillomavirus type 16 (HPV-16) E7 recombinant protein, can augment antitumor immune responses and facilitate tumor eradication. Further mechanistic studies using bone marrow-derived dendritic cells suggest that dtLLO acts as a PAMP by stimulating production of proinflammatory cytokines and inducing maturation of antigen-presenting cells (APC). We propose that dtLLO is an effective adjuvant for tumor immunotherapy, and likely for other therapeutic settings.
MeSH term(s)	Adjuvants, Immunologic/isolation & purification ; Adjuvants, Immunologic/pharmacology ; Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; Bacterial Toxins/isolation & purification ; Bacterial Toxins/pharmacology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Heat-Shock Proteins/isolation & purification ; Heat-Shock Proteins/pharmacology ; Hemolysin Proteins/isolation & purification ; Hemolysin Proteins/pharmacology ; Immunotherapy/methods ; Listeria monocytogenes/chemistry ; Mice ; Mice, Inbred C57BL ; Papillomavirus E7 Proteins/immunology
Chemical Substances	Adjuvants, Immunologic ; Bacterial Toxins ; Cancer Vaccines ; Cytokines ; Heat-Shock Proteins ; Hemolysin Proteins ; Papillomavirus E7 Proteins ; oncogene protein E7, Human papillomavirus type 16 ; hlyA protein, Listeria monocytogenes (R06ZRQ1YX9)
Language	English
Publishing date	2012-11-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2221082-9
ISSN	1556-679X ; 1556-6811
ISSN (online)	1556-679X
ISSN	1556-6811
DOI	10.1128/CVI.00488-12
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Article ; Online: Lm-LLO-Based Immunotherapies and HPV-Associated Disease.

Wallecha, Anu / French, Chris / Petit, Robert / Singh, Reshma / Amin, Ashok / Rothman, John

Journal of oncology

2012 Volume 2012, Page(s) 542851

Abstract: HPV infection is a direct cause of neoplasia and malignancy. Cellular immunologic activity against cells expressing HPV E6 and E7 is sufficient to eliminate the presence of dysplastic or neoplastic tissue driven by HPV infection. Live attenuated Listeria ...

Abstract	HPV infection is a direct cause of neoplasia and malignancy. Cellular immunologic activity against cells expressing HPV E6 and E7 is sufficient to eliminate the presence of dysplastic or neoplastic tissue driven by HPV infection. Live attenuated Listeria monocytogenes- (Lm-) based immunotherapy (ADXS11-001) has been developed for the treatment of HPV-associated diseases. ADXS11-001 secretes an antigen-adjuvant fusion (Lm-LLO) protein consisting of a truncated fragment of the Lm protein listeriolysin O (LLO) fused to HPV-16 E7. In preclinical models, this construct has been found to stimulate immune responses and affect therapeutic outcome. ADXS11-001 is currently being evaluated in Phase 2 clinical trials for cervical intraepithelial neoplasia, cervical cancer, and HPV-positive head and neck cancer. The use of a live attenuated bacterium is a more complex and complete method of cancer immunotherapy, as over millennia Lm has evolved to infect humans and humans have evolved to prevent and reject this infection over millennia. This evolution has resulted in profound pathogen-associated immune mechanisms which are genetically conserved, highly efficacious, resistant to tolerance, and can be uniquely invoked using this novel platform technology.
Language	English
Publishing date	2012-02-02
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2461349-6
ISSN	1687-8469 ; 1687-8450
ISSN (online)	1687-8469
ISSN	1687-8450
DOI	10.1155/2012/542851
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