Technology | Elicera Therapeutics AB

Mode-of-action

CAR T-cell therapy

Treatment with TCR (T-cell receptors)-based therapies and CAR T-cells normally entails extracting and then genetically modifying and expanding the patient’s T-cells before they are returned to the patient intravenously to find and kill cancer cells.

CAR T: The treatment is based on using a chimeric antigen receptor (CAR) that is placed on the surface of the T-cell so that it recognizes a specific target (an antigen) on the tumor cells and can then attack and kill the tumor cells.

The success of CAR T-cell therapies has been remarkable in treatment of hematological cancers and has to date resulted in five market approved products for treating B-cell and plasma cell malignancies. However, no CAR T-cell therapy has yet been approved for treatment of solid tumors.

Challenges for CAR/TCR T-cells in solid tumors

The two main challenges that CAR/TCR T-cell therapies face in the treatment of solid tumors are the heterogenous expression of CAR/TCR target antigens and local immunosuppression that impedes their clinical implementation:

1. CAR/TCR target antigen heterogeneity

Heterogenous antigen expression on tumor cells increases the risk of antigen-escape and the formation of CAR/TCR T-cell resistant tumors.

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2. Immunosuppressive tumor microenvironment

The microenvironment of solid tumors is highly immunosuppressive which both exhausts the CAR/TCR T-cells and makes it more difficult for them to infiltrate tumors, thus inhibiting their potential to kill cancer cells.

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Combating CAR/TCR-target-antigen heterogeneity and reducing immunosuppression within solid tumors, with the help of the iTANK-platform, are of outmost importance for improving CAR/TCR-T therapy.

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iTANK mode-of-action

iTANK CAR/TCR T-cells induce a pro-inflammatory microenvironment and activates the patient’s own killer T-cells against the whole repertoire of relevant tumor antigen targets.

Elicera has developed a technology platform called iTANK (immunotherapies Activated with NAP for efficient Killing) which directly counteracts the two major challenges CAR/TCR T-cell therapies face in treatment of solid tumors. The technology platform arms CAR/TCR T-cells with a pluripotent proinflammatory neutrophil-activating protein (NAP) from Helicobacter pylori which induces bystander immunity via epitope spreading. The system is independent of tumor types and target antigens.

iTANK CAR/TCR T-cells induce a pro-inflammatory microenvironment and activates the patient’s own CD8+ killer T-cells against the whole repertoire of relevant tumor antigen targets.

The NAP is a multifaceted immune activator, able to stimulate other cells to secrete cytokines and chemokines. Using a bacterial derived factor is also more immunogenic and believed to turn the suppressive “cold” environment to “hot”.

iTANK-armed CAR(NAP)-Ts have been shown to:

be more successful in reducing tumor growth and enhancing survival of mice than conventional CAR-Ts.
be more effective in targeting tumors with heterogeneous antigen expression.
create an immunologically hot tumor microenvironment supporting dendritic cell maturation and bystander immunity observed as epitope spreading with infiltration of highly cytolytic proliferative killer T-cells that target tumor-associated antigens other than the CAR target antigen.
Create a pro-inflammatory microenvironment that directly counteracts immunosuppression and enhances the potency of the CAR T-cell.
Be effective in treatment of cancer regardless of the choice of CAR-molecule, tumor type, or mouse model, indicating the platform is universally compatible with other CAR-T technologies.

Watch a presentation of preclinical PoC-data.