Chapter 1 Multiple Effector Mechanisms Induced by Recombinant Listeria monocytogenes Anticancer Immunotherapeutics

Wallecha, Anu; Carroll, Kyla Driscoll; Maciag, Paulo; Rivera, Sandra; Shahabi, Vafa; Paterson, Yvonne

doi:10.1016/s0065-2164(08)00801-0

Cited by 28 publications

(32 citation statements)

References 116 publications

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“…22 Still other effects include Listeria's ability to stimulate myelopoesis and the maturation of immature myeloid cells such as dendritic cell and their ability to facilitate the extravasation of activated immune cells into tumors. 23 In addition to the role of innate immunity stimulated by Listeria-based vaccines, the delivery of a TAA by this vector has a crucial role in its strong and specific antitumor responses. Herein, we also show that ADXS31-164 exerts strong and antigen-specific anti-tumor responses with ability to break immune tolerance toward HER2/ neu in transgenic animals.…”

Section: Discussionmentioning

confidence: 99%

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

et al. 2010

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A chimeric human Her2/neu gene (ChHer2) harboring most of the known major histocompatibility complex class I epitopes of the HER2/neu oncogene was expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O (LLO), by the highly attenuated Listeria vector LmddA, which lacks antibiotic selection markers and the ability to spread from cell-to-cell. This construct (ADXS31-164) was tested for immunogenicity and anti-tumor effects in mice. Despite being highly attenuated, ADXS31-164 proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen. ADXS31-164 elicited strong T-cell immune responses in experimental animals. In tumors, ADXS31-164 caused a reduction in regulatory T cells (Treg) accompanied by an increase in the CD8 þ /Treg ratio. Comparison of this vaccine with the conventional antibiotic resistant Listeria vector (Lm-LLO-ChHer2) shows that ADXS31-164 is more efficacious in delaying tumor growth in Her2/neu transgenic animals. Because of its well-defined attenuation mechanism and independence from antibiotic selection markers, ADXS31-164 is potentially more suitable for human use. These results support the future clinical development of this vaccine for the treatment of HER2/neuoverexpressing malignancies, such as breast, colorectal and pancreatic cancers.

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Section: Discussionmentioning

confidence: 99%

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

et al. 2010

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“…39,40 Boosting with the TAA-based LM vaccine results in activation of memory CD4 and CD8 T-cells to the TAA. Activation of TAA-specific CD8 memory CTL results in the killing of tumor cells through effector CTL-mediated cytolysis and may be enhanced by the activation of memory CD4 T helper cells.…”

Section: Activation Of Adaptive and Innate Immunementioning

confidence: 99%

“…40 Also innate immune responses will be activated by Listeria through the activation of toll-like receptors (TLR) on macrophages and the subsequent production of interleukin (IL)-12, tumor necrosis factor (TNF)α and IL-1. 39,40 These lymphokines attract natural killer (NK) cells and neutrophils to the infection site. IL-12 activates NK cells and T-cells to produce interferon (IFN)γ, which in turn activates bactericidal properties of macrophages, stimulates DC to take up bacterial antigens at the site of infection, and regulates the development of CTL persistence.…”

Section: Activation Of Adaptive and Innate Immunementioning

confidence: 99%

“…In addition, macrophages will be infected with Listeria resulting in strong CTL responses against the highly immunogenic listerial proteins. 39,40 Therefore, it is expected that Listeria-specific CTL will kill the infected tumor cells in vivo. Indeed, depletion of CD8 T-cells in mice that received one preventive and two therapeutic immunizations with LM-LLO showed an increase in tumor growth by 52% compared to LM-LLO alone, suggesting that Listeria-specific CD8 T-cells, at least partially, contribute to tumor reduction in vivo.…”

Section: Tumor Cell Death Mediated By Listeria-specific Ctlmentioning

confidence: 99%

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Harnessing Listeria monocytogenes to target tumors

Gravekamp

Paterson

2010

Cancer Biology & Therapy

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“…Given Listeria's presence in the cytoplasm and the phagolysosome, peptides derived from L monocytogenes can be presented by the MHC class I and class II molecules, inducing both CD4 þ and CD8 þ T-cell-mediated responses. 39,40 The first clinical use of a Listeria-based HPV vaccine was reported by Maciag et al 41 in 2009. The authors studied an HPV-16 E7 antigen fused to a nonhemolytic fragment of the Lm protein LLO (Lm-LLO-E7).…”

Section: Cervical Cancer: Therapeutic Vaccines Bacterial Vectorsmentioning

confidence: 99%

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

Eskander

Tewari

2015

Clinical Therapeutics

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Purpose: In 2014, the US Food and Drug Administration approved the first targeted agent, bevacizumab, in the treatment of advanced stage, persistent, or recurrent cervical cancer. This oncologic milestone has catalyzed interest in the investigation of alternate therapies, including immunotherapy, in an effort to extend life and possibly cure patients with advanced stage disease.Methods: This review article focuses on the evolving paradigm of immunotherapy in the treatment of cervical cancer, describing the biologic basis of this treatment modality and discussing applicable Phase I to II clinical trials.Findings: To date several trials have been conducted exploring vaccine-based therapies, adoptive T-cell therapy, and immune-modulating agents in patients with cervical cancer with promising results.Implications: Immunotherapy represents a promising therapeutic paradigm in the treatment of advanced cervical cancer. Additional investigation is warranted to try and identify alternate immune targets and predictors of response, allowing for the selection of patients most likely to benefit from immune-based treatments. (Clin Ther. 2015;37:20-38) & 2015 Elsevier HS Journals, Inc. All rights reserved.

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Chapter 1 Multiple Effector Mechanisms Induced by Recombinant Listeria monocytogenes Anticancer Immunotherapeutics

Cited by 28 publications

References 116 publications

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

Harnessing Listeria monocytogenes to target tumors

Immunotherapy: An Evolving Paradigm in the Treatment of Advanced Cervical Cancer

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