γδ T Cell Therapy Development for Listeria monocytogenes Infections

Nowadays, immunotherapies based on T cells are becoming a huge trend in the treatment of various diseases including Listeria monocytogenes (L. monocytogenes) infections. Among the various solutions emerging, there is a wave of research focusing on γδ T cells. Creative Biolabs has developed a proprietary and robust process to activate and expand different subsets of γδ T cells to numbers sufficient for utilization in the pre-clinical setting. By using γδ T cells, our technology addresses the challenges that immunotherapies face when targeting L. monocytogenes infection. We also engineer γδ T cells with chimeric antigen receptors (CARs) and T cell receptors (TCRs) to enable the precise engagement and killing of infected cells.

γδ T cells and L. monocytogenes Infections

L. monocytogenes is a gram-positive, intracellular bacterium that causes listeriosis, primarily affecting immunocompromised individuals, newborns and pregnant women. L. monocytogenes replicates inside mononuclear phagocytes and induces specific cellular immunity and can cross the blood-brain barrier (BBB), intestinal barrier, or feto-placental barrier and lead to serious infectious illness and death in different populations. L. monocytogenes is the only pathogenic bacterium known to contain both mevalonate and nonmeva-lonate pathways of isoprenoid biosynthesis, concurrently producing metabolites such as HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate) and isopentenyl pyrophosphate (IPP) which are the specific ligands of γδ TCR. Human α/β and γδ T cells have been shown to respond to L. monocytogenes antigens and to play an important role in resistance against listerial infection.

Fig.1 Successive steps of human listeriosis. (Cossart, 2008)

γδ T Cell Therapy for L. monocytogenes Infections

IL-17A is mainly produced by γδ T cells during L. monocytogenes infection to promote innate and adaptive immune responses, and it promotes host function of effective elimination of infection by producing cytokines and CXC chemokines. In the early infective stage in the liver of mouse models, IL-17A produced by γδ T cells enhances the antibacterial activity of nonphagocytic cells infected by L. monocytogenes. Besides, the IL-17A-producing γδ T cells, which are activated rapidly following L. monocytogenes infection, mediate its antibacterial immune response via IL-23 production by pathogen-activated macrophages and DCs during the early phase of infection.

Collectively, innate IL-17A could induce the proliferation of cytotoxic T cells and play their effective cytotoxic T cell response to eliminate L. monocytogenes. Besides, IL-17A also plays a critical role in controlling intestinal pathogens during secondary L. monocytogenes infection. L. monocytogenes-specific memory γδ T cells represent a resident memory (Trm) population in the mesenteric lymph node that secretes IL-17A and cluster with L. monocytogenes replication foci after secondary infection. Findings from reported in vitro experiments proved that γδ T cells have an internalizing capability when bound to L. monocytogenes and induce a specific immune response to L. monocytogenes. This indicates that γδ T cells serve as antigen presenting cells (APCs) during L. monocytogenes infection.

What Can We Do for You?

Creative Biolabs provides different γδ T cell services and various products for L. monocytogenes infection for worldwide customers, including but not limited to:

• γδ T Cell Receptors Services
• γδ T Cell Development
• γδ T Cell Engineering

Creative Biolabs keeps in a leading position and has gained rich experience in the academic area of γδ T immunotherapy. We are proud to successfully operate an advanced platform to combine chimeric antigen receptor (CAR) service with γδ T cell for therapeutic. This technology enables patients to kill tumor cells and eliminate infected cells with their own T-cells more effectively. We specialize in γδ research project design and execution. For any questions, please contact us for more information.

Reference

1. Cossart, P.; and Toledo-Arana, A. Listeria monocytogenes, a unique model in infection biology: an overview. Microbes and Infection. 2008, 9(10): 1041-1050.