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CellRapeutics™ Chimeric Engulfment Receptor (CER) Technology

Chimeric antigen receptors (CARs) are designed to attach to specific proteins to reprogram T cells to kill cancer. The success of CAR-T cell therapy highlights the prospect of programmed immunity and suggests that applying CAR strategies to other immune cell lineages may be beneficial. As a leading technology provider, Creative Biolabs has established the CellRapeutics™ chimeric engulfment receptor (CER) technology platform for phagocytosis, which directs macrophages to engulf specific targets on cancer cells.

Significance of Macrophage-mediated Phagocytosis

Macrophages are a key effector of the innate immune system and are responsible for engulfing debris and pathogens. A variety of evidence shows that macrophages have the unique ability to penetrate solid tumors and fight tumor growth, while other immune cells (such as T cells) are physically rejected or inactivated. This suggests that engineered macrophages may enhance existing T cell-based cell therapies.

Another supporting finding is that antibody blocking of the negative regulator of phagocytosis, CD47, reduces tumor burden, suggesting that metastatic balance to promote macrophage activation and phagocytosis is a promising therapeutic approach. Therefore, our innovative CER-macrophage therapy holds broad therapeutic prospects in the future.

Role of tumor-associated macrophages (TAMs) in cancer.

Fig.1 Role of tumor-associated macrophages (TAMs) in cancer.

CER Design and Construction

We have developed different generations of CERs. Similar to CAR, our CERs essentially consist of three modules: the extracellular domain targeting (ECD) targeting the phagocytic target antigen, transmembrane domain (TMD) and phagocytosis intracellular signaling domain (ESD). The ECD protein can be scFv, Fab, VHH, peptide, or sometimes an FcR. The ESD of our second-generation CER includes a primary phagocytic signal domain and a secondary phagocytic signal domain.

Schematic of the structure of CER constructs

Fig.2 Schematic of the structure of CER constructs.

One-stop CER-MA Development Services

Empowered by our high qualified groups and advanced technologies, Creative Biolabs provides one-stop CER-MA development services:

CellRapeutics™ Chimeric Engulfment Receptor (CER) Technology

It should be noted that our CER can not only genetically modify macrophages, but also modify the phagocytic phenotype of cells that do not naturally show phagocytic activity, including T cells, natural killer cells, natural killer T cells, B cells, somatic cells, dendritic cells, Langerhans cells, and bone marrow cells.

For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Meghan A Morrissey.; et al. Chimeric antigen receptors that trigger phagocytosis. SHORT REPORT. Jun 4, 2018.

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