Attenuated Listeria monocytogenes vaccine vector (Lm)

Molecular Classification

Other (not a receptor, enzyme, transporter, or ion channel; acts as a whole-cell microbial vector), Vaccine vector, Live attenuated microbial vector

Other Names

Attenuated Lm, Listeria vaccine vector, Lm-based immunotherapy, Listeria monocytogenes vaccine, recombinant Listeria monocytogenes

Disease Roles

Cancer (as immunotherapy for various malignancies)Infection (vaccine platform for infectious diseases)Other (potential roles in modulating inflammation or autoimmune responses)

Attenuated Listeria monocytogenes vaccine vector Overview

Attenuated Listeria monocytogenes vaccine vectors are genetically modified strains of the bacterium Listeria monocytogenes, engineered for safety by deleting key virulence genes. As a live microbial vector, Lm can infect antigen-presenting cells, deliver tumor- or pathogen-associated antigens directly into the cytosol, and stimulate potent, cell-mediated immune responses. Prominent in cancer immunotherapy, Lm vectors increase infiltration and activity of effector T cells, reduce immunosuppressive populations in the tumor microenvironment, and can be further combined with other treatments (such as checkpoint blockade) to enhance antitumor immunity. Safety is managed by attenuation strategies, with ongoing research aimed at balancing immunogenicity and safety, as well as optimizing antigen delivery.

Mechanism of Action

Delivery of antigens via intracellular infection of APCs, leading to antigen presentation through MHC class I and II pathways; Stimulation of robust cytotoxic T lymphocyte (CTL) and helper T cell responses; Reduction in immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs); Polarization of tumor-associated macrophages towards an anti-tumor phenotype

Biological Functions

Immune response activation (by stimulating cellular and humoral immunity)

Induction of antigen-specific T cell responses (both CD8+ cytotoxic and CD4+ helper)

Tumor microenvironment modulation (increases effector T cells, reduces immunosuppressive cells)

Antigen delivery to antigen-presenting cells (APCs)

Disease Associations

Cancer (as immunotherapy for various malignancies)

Infection (vaccine platform for infectious diseases)

Other (potential roles in modulating inflammation or autoimmune responses)

Safety Considerations

Risk of infection in immunocompromised patients (mitigated by attenuation strategies such as deletion of virulence genes like actA, prfA, inlB)
Potential for early immune clearance (anti-vector immunity limits efficacy)
Systemic toxicity/toxic shock in rare cases (liver toxicity mitigated by attenuation)
Limited persistence in vivo (sometimes desirable for safety, but may limit immune stimulation efficacy)
Need for rigorous assessment in combinatorial regimens

Interacting Drugs

Currently, specific "drugs" interacting with this target are primarily vaccines engineered using Listeria monocytogenes expressing tumor antigens or pathogen-derived antigens (e.g., PSA, HPV E6/E7)

Combinatorial regimens may include checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4), and radiotherapy

Associated Biomarkers

Biomarker
Increased effector CD8+ T cells (e.g., IFN-γ-producing T cells)
Decrease in FoxP3+ regulatory T cells
Induction of antigen-specific immune responses (e.g., PSA-specific T cells, HPV E6E7-specific T cells)
Expression of interferon-stimulated gene 15 (ISG15)