Technology

Scientific Publications

The following representative publications from the peer-reviewed literature further discuss the scientific principles around which Advaxis has built its platform research technology.

Key Publications

Episomal expression of a truncated listeriolysin O in LmddA-LLO-E7 vaccine enhances anti-tumor efficacy by preferentially inducing CD4+FoxP3- T cell and CD8+ T cell expansion
Zhisong Chen, Laurent Ozbun, Namju Chong, Anu Wallecha, Jay A Berzofsky, and Samir N Khleif. American Association for Cancer Research, [2013]

Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of Myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment
Wallecha A, et al. Journal of Immunotherapy of Cancer 2013, 1(Suppl 1):O18 (7 November 2013)

ADXS11-001 immunotherapy targeting HPV-E7: preliminary survival data from a phase 2 study in Indian women with recurrent/refractory cervical cancer
Petit R., Basu P., et al.

Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
Mkrtichyan M, Chong N, Abu Eid R, Wallecha A, Singh R, Rothman J and Khleif SN Journal for ImmunoTherapy of Cancer 2013, 1:15 (29 August 2013)

Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular pattern-like properties independent of its hemolytic ability
Wallecha A, Wood L, Pan ZK, Maciag PC, Shahabi V, Paterson Y. Clin Vaccine Immunol. 2013 Jan;20(1):77-84

Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer.
Hannan R, Zhang H, Wallecha A, Singh R, Liu L, Cohen P, Alfieri A, Rothman J. Guha C. Cancer Immunol Immunother. 2012 Dec;61(12):2227-38.

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human
Shahabi V, et al. Cancer Gene Ther. 2010.

The first clinical use of a live-attenuated Listeria monocytogenes vaccine: a Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix
Maciag PC, et al. Vaccine, 2009, 27(30):3975-3983.

A novel human Her-2/neu chimeric molecule expressed by Listeria monocytogenes can elicit potent HLA-A2 restricted CD8-positive T cell responses and impact the growth and spread of Her-2/neu-positive breast tumors
Seavey MM, et al. Clin Cancer Res. 2009, 15(3):924-932.

Construction and characterization of an attenuated Listeria monocytogenes strain for clinical use in cancer immunotherapy
Wallecha A, et al. Clin Vaccine Immunol. 2009, 16(1):96-103.

An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytgenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu+ breast tuomors in a mouse model
Seavey MM, et al. J Immunol. 2009, 182(9):5537-5546.

Multiple effector mechanisms induced by recombinant Listeria monocytogenes anticancer immunotherapeutics
Wallecha A, et al. Adv Appl Microbiol. 2009, 66:1-27.

Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors
Sewell DA, et al. Vaccine. 2008, 26(41):5315-5320.

Development of a Listeria monocytogenes based vaccine against prostate cancer
Shahabi V, et al. Cancer Immunol Immunother. 2008, 57(9):1301-1313.

Cancer immunotherapy targeting the high molecular weight melanoma-associated antigen protein results in a broad antitumor response and reduction of pericytes in the tumor vasculature.
Maciag PC, Seavey MM, Pan ZK, Ferrone S, Paterson Y. Cancer Res. 2008 Oct 1;68(19):8066-75

Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors.
Wood LM, et al. Immunol Res. 2008. 42(1-3):233-245.

Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16
Gunn GR, et al. J Immunol. 2001, 167(11):6471-6479.

Immune Response and Immunotherapy: Live Attenuated Listeria monocytogenes (Lm)-LLO Immunotherapy for the Treatment of Prostate Cancer
Wallecha A, et al. Current Cancer Therapy Reviews, 2012, 8, 254-263

Lm-LLO-Based Immunotherapies and HPV-Associated Disease
Wallecha A, et al. Journal of Oncology, Volume 2012, Article ID 542851

Clinical Studies

Preclinical Studies/Combination with Other Therapies

Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
Mkrtichyan M, Chong N, Abu Eid R, Wallecha A, Singh R, Rothman J and Khleif SN Journal for ImmunoTherapy of Cancer 2013, 1:15 (29 August 2013)

Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer.
Hannan R, Zhang H, Wallecha A, Singh R, Liu L, Cohen P, Alfieri A, Rothman J. Guha C. Cancer Immunol Immunother. 2012 Dec;61(12):2227-38.

Anti-tumor Immunotherapy

The ubiquitin-like protein, ISG15, is a novel tumor-associated antigen for cancer immunotherapy
Wood LM, Pan ZK, Seavey MM, Muthukumaran G, Paterson Y. Cancer Immunol Immunother. 2011 Nov 6.

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human
Shahabi V, et al. Cancer Gene Ther. 2010.

Listeria-derived ActA is an effective adjuvant for primary and metastatic tumor immunotherapy
Wood LM, et al. Cancer Immunol Immunother. 2010.

High efficacy of a Listeria-based vaccine against metastatic breast cancer reveals a dual mode of action
Kim SH, et al. Cancer Res. 2009, 69(14):5860-5866.

An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytgenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2/neu+ breast tuomors in a mouse model
Seavey MM, et al. J Immunol. 2009, 182(9):5537-5546.

A novel human Her-2/neu chimeric molecule expressed by Listeria monocytogenes can elicit potent HLA-A2 restricted CD8-positive T cell responses and impact the growth and spread of Her-2/neu-positive breast tumors
Seavey MM, et al. Clin Cancer Res. 2009, 15(3):924-932.

Construction and characterization of an attenuated Listeria monocytogenes strain for clinical use in cancer immunotherapy
Wallecha A, et al. Clin Vaccine Immunol. 2009, 16(1):96-103.

Development of a Listeria monocytogenes based vaccine against prostate cancer
Shahabi V, et al. Cancer Immunol Immunother. 2008, 57(9):1301-1313.

Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors
Sewell DA, et al. Vaccine. 2008, 26(41):5315-5320.

Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases
Kim SH, et al. Br J Cancer. 2008, 99(5):741-749.

In the FVB/N HER-2/neu transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by Listeria monocytogenes-based vaccines
Singh R and Paterson Y. Cancer Immunol Immunother. 2007, 56(6):927-938.

Listeria-based vaccines can overcome tolerance by expanding low avidity CD8+ T cells capable of eradicating a solid tumor in a transgenic mouse model of cancer
Souders NC, et al. Cancer Immun. 2007, 7:2.

Fusion to Listeriolysin O and delivery by Listeria monocytogenes enhances the immunogenicity of HER-2/neu and reveals subdominant epitopes in the FVB/N mouse
Singh R, et al. J Immunol. 2005, 175(6):3663-­3673.

Recombinant Listeria vaccines containing PEST sequences are potent immune adjuvants for the tumor-associated antigen human papillomavirus-16 E7
Sewell DA, et al. Cancer Res. 2004, 64(24):8821-8825.

Regression of HPV-positive tumors treated with a new Listeria monocytogenes vaccine
Sewell DA, et al. Arch Otolaryngol Head Neck Surg. 2004, 130(1):92-97.

Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16
Gunn GR, et al. J Immunol. 2001, 167(11):6471-6479.

The tumor recall response of antitumor immunity primed by a live, recombinant Listeria monocytogenes vaccine comprises multiple effector mechanisms
Weiskirch LM, et al. Clin Immunol. 2001, 98(3):346-357.

A recombinant Listeria monocytogenes vaccine expressing a model tumor antigen protects mice against lethal tumour cell challenge and causes regression of established tumours
Pan ZK, et al. Nat Med. 1995, 1(5):471-477.

Reduction of Immunosuppression

Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy
Mkrtichyan M, Chong N, Abu Eid R, Wallecha A, Singh R, Rothman J and Khleif SN Journal for ImmunoTherapy of Cancer 2013, 1:15 (29 August 2013)

Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice.
Chandra D, Jahangir A, Quispe-Tintaya W, Einstein MH, Gravekamp C. Br J Cancer. 2013 Jun 11;108(11):2281-90

Construction and characterization of an attenuated Listeria monocytogenes strain for clinical use in cancer immunotherapy
Wallecha A, et al. Clin Vaccine Immunol. 2009, 16(1):96-103.

Development of a Listeria monocytogenes based vaccine against prostate cancer
Shahabi V, et al. Cancer Immunol Immunother. 2008, 57(9):1301-1313.

CD4+CD25+ regulatory T cells that secrete TGFbeta and IL-10 are preferentially induced by a vaccine vector
Hussain SF, et al. J Immunother. 2004, 27(5):339-346.

Alteration of Vasculature, Stromal Effects, and Cytokine Production

Listeria monocytogenes-derived listeriolysin O has pathogen-associated molecular pattern-like properties independent of its hemolytic ability
Wallecha A, Wood L, Pan ZK, Maciag PC, Shahabi V, Paterson Y. Clin Vaccine Immunol. 2013 Jan;20(1):77-84

Vaccination with immunotherapeutic Listeria monocytogenes induces IL-17(+) γδ T cells in a murine model for HPV associated cancer
Guirnalda PD, Paterson Y. Oncoimmunology. 2012 Sep 1;1(6):822-828.

Targeting tumor vasculature with novel Listeria-based vaccines directed against CD105
Wood LM, Pan ZK, Guirnalda P, Tsai P, Seavey M, Paterson Y.

An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine or the treatment of primary and metastatic Her-2/neu+ breast tumors in a mouse model
Seavey MM, et al. J Immunol. 2009, 182(9):5537-5546.

The ability of two Listeria monocytogenes vaccines targeting human papillomavirus-16 E7 to induce an antitumor response correlates with myeloid dendritic cell function
Peng X, et al. J Immunol. 2004, 172(10):6030-6038.

Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16
Gunn GR, et al. J Immunol. 2001, 167(11):6471-6479.

The tumor recall response of antitumor immunity primed by a live, recombinant Listeria monocytogenes vaccine comprises multiple effector mechanisms
Weiskirch LM, et al. Clin Immunol. 2001, 98(3)346-357.

Regression of established B16F10 melanoma with a recombinant Listeria monocytogenes vaccine
Pan ZK, et al. Cancer Res. 1999, 59(20):5264-5269.

Strains, Constructs, and Techniques

Effect of a novel DNA vaccine on angiogenesis and tumor growth in vivo
McKinney KA, et al. Arch Otolaryngol Head Neck Surg. 2010, 136(9):859-864.

Construction and characterization of an attenuated Listeria monocytogenes strain for clinical use in cancer immunotherapy
Wallecha A, et al. Clin Vaccine Immunol. 2009, 16(1):6-103.

Listeria monocytogenes-based antibiotic resistance gene-free antigen delivery system applicable to other bacterial vectors and DNA vaccines
Verch T, et al. Infect Immun. 2004, 72(11):6418-6425.

Enhancing the immunogenicity of bioengineered Listeria monocytogenes by passaging through live animal hosts
Peters C and Paterson Y. Vaccine. 2003, 21(11-12):1187-1194.

Two Listeria monocytogenes vaccine vectors that express different molecular forms of human papilloma virus-16 (HPV-16) E7 induce qualitatively different T cell immunity that correlates with their ability to induce regression of established tumors immortalized by HPV-16
Gunn GR, et al. J Immunol. 2001, 167(11):6471-6479.

Studies in Transgenic Mice/Tolerance Systems

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human
Shahabi V, et al. Cancer Gene Ther. 2010.

A novel human Her-2/neu chimerical molecule expressed by Listeria monocytogenes can elicit potent HLA-A2 restricted CD8-positive T cell responses and impact the growth and spread of Her-2/neu-positive breast tumors
Seavey MM, et al. Clin Cancer Res. 2009, 15(3):924-932.

An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the
treatment of primary and metastatic Her-2/neu+ breast tumors in a mouse model

Seavey MM, et al. J Immunol. 2009, 182(9):5537-5546.

Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors
Sewell DA, et al. Vaccine. 2008, 26(41):5315-5320.

In the FVB/N HER-2/neu transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by Listeria monocytogenes-based vaccines
Singh R and Paterson Y. Cancer Imunol Immunother. 2007, 56(6):927-938

Listeria-based vaccines can overcome tolerance by expanding low avidity CD8+ T cells capable of eradicating a solid tumor in a transgenic mouse model of cancer
Souders NC, et al. Cancer Immun. 2007, 7:2.

Epitope Spreading

Reviews

Live-attenuated Listeria-based immunotherapy.
Rothman J, Paterson Y. Expert Rev Vaccines. 2013 May;12(5):493-504.

Listeria monocytogenes and its products as agents for cancer immunotherapy.
Guirnalda P, Wood L, Paterson Y. Adv Immunol. 2012;113:81-118.

Cancer immunotherapy using recombinant Listeria monocytogenes: Transition from bench to clinic
Singh R and Wallecha A. Hum Vaccine. 2011. 7(5).

Listeria and Salmonella bacterial vectors of tumor-associated antigens for cancer immunotherapy
Paterson Y, Guirnalda PD, Wood LM. Semin Immunol. 2010 Jun;22(3):183-9.

Multiple effector mechanisms induced by recombinant Listeria monocytogenes anticancer immunotherapeutics
Wallecha A, et al. Adv Appl Microbiol. 2009, 66:1-27.

Cancer immunotherapy using Listeria monocytogenes and listerial virulence factors.
Wood LM, et al. Immunol Res. 2008. 42(1-3):233-245.

Listeria monocytogenes as a vector for tumor-associated antigens for cancer immunotherapy
Singh R and Paterson Y. Expert Rev Vaccines. 2006, 5(4):541-552.

What is needed for effective antitumor immunotherapy? Lessons learned using Listeria monocytogenes as a live vector for HPV-associated tumors
Hussain SF and Paterson Y. 2005, 54(6):577-586.

Listeria-based vaccines for cancer treatment
Paterson Y and Maciag PC. Curr Opin Mol Ther. 2005, 7(5):454-460.

Infectious Disease Publications

Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice.
Shollenberger LM, Bui C, Paterson Y, Allen K, Harn D. Vaccine. 2013 Apr 12;31(16):2050-6

A DNA prime-oral Listeria boost vaccine in rhesus macaques induces a SIV-specific CD8 T cell mucosal response characterized by high levels of alpha4beta7 integrin and an effector memory phenotype
Neeson P, et al. Virology. 2006, 354(2):299-315.

DNA prime Listeria boost induces a cellular immune response to SIV antigens in the rhesus macaque model that is capable of limited suppression of SIV239 viral replication
Boyer JD, et al. Virology. 2005, 333(1):88-101

Progress towards the use of Listeria monocytogenes as a live bacterial vaccine vector for the delivery of HIV antigens
Paterson Y and Johnson RS. Expert Rev Vaccines. 2004, 3(4 Suppl):S119-134.

The induction of HIV Gag-specific CD8+ T cells in the spleen and gut-associated lymphoid tissue by parenteral or mucosal immunization with recombinant Listeria monocytogenes HIV Gag
Peters C, et al. J Immunol. 2003, 170(10):5176-5187

Evaluation of a recombinant Listeria monocytogenes expressing an HIV protein that protects mice against viral challenge
Mata M, et al. Vaccine. 2001, 19(11-12):434-1445.

Th1 T cell responses to HIV-1 Gag protein delivered by a Listeria monocytogenes vaccine are similar to those induced by endogenous listerial antigens
Mata M and Paterson Y. J Immunol. 1999, 163(3):1449-1456.