Macrophages

Tumor microenvironment (TME) is a complex and continuously evolving structure around tumor cells consisting of innate and adaptive immune cells, stromal cells and new microvessels. Macrophages, differentiating from monocytes, are attracted by chemokines and cytokines secreted by tumor cells and naturally migrate to solid tumors. Macrophage infiltration is particularly high in solid tumors with aggressive behavior and poor prognosis. Their number is four times higher than T cells in glioblastoma and two times higher in ovarian cancer and lung cancer.

In cancer patients, monocytes extravasate and migrate to hypoxic vascular tumor areas and differentiate into macrophages. By releasing multiple immunosuppressive cytokines, growth factors, and metalloproteinases macrophages facilitate tumor angiogenesis, invasion, and metastasis. Due to the complexity of the TME and dense extracellular matrix, currently available therapies are inefficient.

MDC – Macrophage-Drug Conjugate is the macrophage (autologous or allogeneic) loaded with a ferritin-drug complex. This smart immune-therapy targets solid tumors of unmet medical needs.

MDC may contain a range variety of compounds: immunomodulators, inhibitors, cytotoxic drugs, radioisotopes, and peptides.

TRAIN

Cellis team has discovered a new physiological phenomenon that have been named TRAnsfer of Iron-binding proteiN (TRAIN) and which is exploited in cutting-edge MDC technology.

MDCs show high ability in tumor homing and instant unloading features making delivery of selected compounds very efficient. This makes MDC an interesting approach in both oncology and inflammation.

MDC are unmodified genetically and may be applied as autologous or allogeneic therapy. Allogeneic therapy has the potential to reduce complexity and the currently access-limiting logistical challenges in cell-based treatment.

Macrophage therapy

Our MDC technology addresses limitations of current solid tumor treatment options: lack of specificity, on-target off-tumor toxicity, low tumor penetration particularly to the hypoxic regions, and inadequate penetration to metastases.

Cellis has demonstrated preclinical proof-of-concept with multiple MDCs. In addition, Cellis validated the platform in numerous preclinical animal models of solid cancers. In those models, MDCs showed increases survival, tumor shrinkage, and reduction in metastases.