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Laboratory

Our work

Image by National Cancer Institute

Novel CAR iNKT cells.

Utilizing NKTFH cells to improve lung vaccinations.

NKT10 cells as cellular therapy to suppress autoimmune diseases.

Our current focus is iNKT cells with these projects under development:

Embryonic Stem Cells

CAR iNKT cells

T cells are essential players in the anti-tumour response and almost all aberrant cells are eliminated by the immune system. However, in cancer patients, the tumour developed means to inactivate the attacking T cells. A highly efficient anti-cancer therapy is to engineer conventional T cells of the patient in vitro to express a novel receptor that allows the T cells to target the cancer cells anew. Such chimeric antigen receptors (CARs) enable the engineered CAR T cells to recognize specifically the tumour and to be strongly activated in the process. However, CAR T cells derived from conventional T cells have several drawbacks and prominent among those is the need to generate CAR T cells specifically for every individual patient as CAR T cells from another person could potentially attack the patient, a complication called GvHD (graft-versus-host-disease).

Due to their unique properties, iNKT cells cannot induce GvHD. Furthermore, CAR iNKT cells bear several other advantages over CAR T cells, making them promising alternatives for CAR T cells.

The initial target for the CAR iNKT cells we develop is melanomas, a form of skin cancer.

NKTFH cells

Vaccinations protect us against future infections by training the immune system on how to fight a particular pathogen. To this end, vaccines contain at least two elements. One element resembles a piece of the pathogen which the immune system learns to recognize and remember. The second element is a compound which tells the immune system that a strong response and a good memory are needed. This element is called an adjuvant, from the Latin word for ‘to help’.

The most effective vaccines activate both arms of the adaptive immune system, B and T cells. B cells produce the antibodies that protect the body against future infections. For this, the B cells need the support of T cells specialized in helping B cells, called TFH (T follicular helper) cells. The stronger the support of the TFH cells for the B cells (also called B cell-help), the stronger the antibody response. However, like other conventional T cells, these TFH cells need up to one week to develop and gain their functions. In contrast, iNKT cells, due to their innate-like features, need only 2-3 days to differentiate into B cell-helpers, also called NKTFH cells. Therefore, NKTFH cells can jump-start the B cell response before TFH cells develop.

Meriel Biosciences aims to develop tools that are most efficient at inducing NKTFH cells in vivo and which can be included in vaccines to improve the antibody response.

NKT10 cells

The immune system requires a delicate balance between pro-inflammatory responses, which protect us e.g. against pathogens, and anti-inflammatory responses, which avoid e.g. tissue damage. Autoimmune diseases occur when this balance is disturbed and the adaptive immune system (B and T cells) attacks the host. Most current therapies for autoimmune disease suppress these attacking cells but these leave the patients vulnerable to e.g. infections. A more promising approach is to strengthen the anti-inflammatory response and reestablish self-tolerance. To this end, regulatory T cells (Tregs), which are anti-inflammatory conventional T cells, are tested in clinical trials with promising results. However, the regulation of Tregs is highly complex and as they differ in every human, the therapy needs to be adjusted to every individual patient.

Team members of Meriel Biosciences discovered anti-inflammatory NKT10 cells and we believe that their innate-like properties avoid the problems experienced with Tregs. We are currently optimizing the protocols for the in vitro expansion of human NKT10 cells to allow clinical trials.

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