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

Listeria vaccines join the checkpoint frenzy
Gunjan Sinha. Nature Biotechnology (9 December 2014)

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.