Allogeneic Macrophages for Cancer Therapy

Introduction

Macrophage cell therapy can become an attractive example of a cell therapy, with numerous potential applications, among them cancer therapy. While T-cell based therapies – so successful for the treatment of hematological malignancies! – have yet to demonstrate effectiveness in the treatment of solid tumors, macrophages are a key component of the tumor microenvironment (TME), and in principle, they are capable of killing solid tumor cells.

Challenges in Macrophage Cell Therapy

However, wildtype macrophages commonly respond to the TME by acquisition of a M2-like polarization state. In this state, they rather support tumor growth and metastatic spread. This is a first problem for macrophage cell therapy against cancer.

Limitations of Human Macrophages

Besides, unlike T-cells, human macrophages cannot be expanded in cell culture, resulting in insufficient numbers of obtainable macrophages and thus limiting their utility for cell therapy.

Innovative Approach

We have generated genetically engineered human macrophages, which have proliferative potential, are resistant to tumor-induced repolarization, and thus demonstrate oncolytic activity. We want to translate these exciting findings into a cell therapy against cancer.

Project Overview: ONCOMAC

ONCOMAC relates to the preparation for and design of a preclinical proof-of-concept study for these genetically engineered human macrophages, so that we will have a sound basis for the translation of our genetically engineered macrophages into clinical trials.

Regulatory Compliance

In particular, ONCOMAC will establish the numerous complex analytical procedures which are required by the European Medicine Agency's regulatory framework for “First-in-human” studies of an ATMP (Advanced Therapy Medicinal Product).