Efficacy boost for dendritic cell therapies

Dendritic cells (DCs) present antigens and thus can activate T-cells for a specific immune response, e.g. against tumor cells or infectious microbes. Autologous DCs for tumor immunotherapies are generated from patient’s blood before being matured, loaded with tumor antigens ex vivo and finally transferred back into the patient to provoke a systemic anti-tumor response.

Maturation or activation of the DCs is a critical step for DC tumor immunotherapy, because it is directly related to the DC’s T-Cell priming capacity. Therefore, a protocol for improved DC activation could strongly increase the efficacy of existing DC-based therapies.

The innovation describes the use of the enzyme galactose oxidase (GOX) to improve the immunogenicity of DCs. This leads to a stronger physical interaction between DCs and T cells, resulting in an up to 10-fold improved T cell priming capacity. In vitro assays (mouse & human) showed strongly enhanced T cell priming potential and T cell proliferation when using GOX-treated DCs, and mice treated with a corresponding DC therapy showed markedly reduced tumor growth and better survival compared to DC treatment without prior GOX-based activation. In addition, low-affinity T cells, which are usually unresponsive and thus are a common challenge for immune therapies with (self)-tumor antigens, can be activated by GOX-treated DCs, resulting in a highly improved anti-tumor response.

The innovation can markedly improve existing DC-based cell therapies, for example in tumor or HIV treatments.

Proof of concept. In vitro mouse and human data, in vivo mouse data.