Cancer immunotherapy using recombinant<i>Listeria monocytogenes</i>: Transition from bench to clinic

Singh, Ram; Wallecha, Anu

doi:10.4161/hv.7.5.15132

Cited by 29 publications

(18 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various methods of bioengineering allow Lm to express TSA on the plasmid or in the genome via chromosomal insertion [23, 24]. At Advaxis, two complementation mechanisms have been designed for the in vivo retention of plasmids in attenuated bacterial strains.…”

Section: Listeria Monocytogenes (Lm): a Potent Vector For Immunothmentioning

confidence: 99%

Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Wallecha

French

Petit

et al. 2012

Journal of Oncology

Self Cite

View full text Add to dashboard Cite

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 attenuatedListeria 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 theLmprotein 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 millenniaLmhas 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.

show abstract

Section: Listeria Monocytogenes (Lm): a Potent Vector For Immunothmentioning

confidence: 99%

Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Wallecha

French

Petit

et al. 2012

Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Briefly, the attenuated Lm expressing the HPV antigen fused to LLO is taken up by antigen-presenting cells via phagocytosis [33, 34]. Through its induction of pro-inflammatory cytokines from natural killer cells, recruitment of monocytes from the peripheral blood to the site of inflammation, and maturation of local dendritic cells, LLO helps to mediate a number of immunostimulatory effects that are an essential bridge between the innate and adaptive immune responses [33].…”

Section: Reviewmentioning

confidence: 99%

“…The immunogenic nature of LLO is further associated with a peptide sequence rich in proline, glutamic acid, serine, and threonine, which likely targets the protein for rapid ubiquitin-mediated proteasomal degradation, with antigenic fragments processed via this cytosolic pathway and subsequently presented via MHC class I to antigen-specific CD8+ T cells. Thus, both arms of the adaptive immune system are stimulated, resulting in the generation of strong T-cell–mediated effector immune responses and protective immunity [33, 34]. …”

Section: Reviewmentioning

confidence: 99%

Mechanistic insights into ADXS11-001 human papillomavirus-associated cancer immunotherapy

Miles

Monk

Safran

2017

gynaecol oncol res pract

View full text Add to dashboard Cite

Immune responses to the facultative intracellular bacterium Listeria monocytogenes (Lm) are robust and well characterized. Utilized for decades as a model of host-disease immunology, Lm is well suited for use as an immunotherapeutic bacterial vector for the delivery of foreign antigen. Genetic modification of Lm has been undertaken to create an attenuated organism that is deficient in its master transcriptional regulator, protein-related factor A, and incorporates a truncated, nonhemolytic version of the listeriolysin O (LLO) molecule to ensure its adjuvant properties while also preventing escape of the live organism from the phagolysosome. Delivery of a vaccine construct (Lm-LLO-E7; axalimogene filolisbac [AXAL] or ADXS11-001) in which the modified LLO molecule is fused with the E7 oncoprotein of human papillomavirus type 16 (HPV-16) consistently stimulates strong innate and E7 antigen-specific adaptive immune responses, resulting in reduction of tumor burden in animal cancer models. In the clinical setting, AXAL has shown early promise in phase I/II trials of women with cervical cancer, and several more trials are currently underway to assess the efficacy and safety of this antitumor vaccine in patients with HPV-positive head and neck and anal cancers.

show abstract

“…In addition, the administration of Lm-vectored vaccines in immune-compromised or -suppressed patients, including the very young, the elderly and pregnant women, can have serious consequences, such that the use of these vaccines may be inappropriate for these populations. 33 To circumvent this problem, there may be many methods to ameliorate the effect of Lm-based vaccination to avoid potential impairment, such as the adoption of heterologous immunization regimens that involve priming with a DNA vaccine and subsequent boosting with Listeria. However, we may be neglecting one important advantage of Lm-based anti-tumor vaccines, the virulence factor LLO.…”

Section: Listeriolysin O As a Strong Immunogenic Molecule For The Devmentioning

confidence: 99%

Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines

Sun

Liu

2013

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Cancer immunotherapy using recombinantListeria monocytogenes: Transition from bench to clinic

Cited by 29 publications

References 66 publications

Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Mechanistic insights into ADXS11-001 human papillomavirus-associated cancer immunotherapy

Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines

Contact Info

Product

Resources

About