Immunotherapy Using Reprogrammed Macrophage Cells

Antibodies that reprogram a type of macrophage cell in cancer tumors, making the immune system better able to recognise and kill tumor cells, have been generated by researchers at Karolinska Institutet. The study could lead to a new therapy and provide a potentially important diagnostic tool for breast cancer and malignant melanoma.

Immunotherapy enhances the immune system in order to kill tumour cells, especially the kind designed to activate the immune system. It is changing the way we treat cancer, since unlike other forms of cancer therapy, immunotherapy targets not the tumor itself but specific cells in the immune system to unleash the ability of the immune system to kill the tumor.

Research team member Mikael Karlsson at the Department of Microbiology, Tumor and Cell Biology, said:

“We’ve found a new way of using antibodies for immunotherapy that activates immune cells, called macrophages, in the tumour. This makes it easier for the immune system to recognise the tumor and animal studies of three different cancers have given promising results.”

Antibodies that increase the ability of T-cells to kill tumor cells have proved particularly effective and created new opportunities for treating previously untreatable cancer.

Not Sufficiently Effective

However, for some patients, T-cell modified immunotherapy has not been sufficiently effective, as some tumors still manage to conceal themselves from the immune system by emitting signals that prevent the immune cells from recognising them. Another reason for the occasional failure of the therapy is that tumors do not trigger as strong an immune reaction as, for example, infections do.

So the researchers focused on macrophages, immune cells whose normal function is to combat infection.

Some macrophages, however, affect their environment in the tumor in a way that makes it easier for cancer cells to survive and spread. Commonly dominant in tumors is a type of macrophage that prevents T-cells and other immune cells from recognising and killing cancer cells.

Stopped Tumors

The researchers managed to reprogram and activate these macrophages by using an antibody targeted at a protein on their cell surface, which stopped the tumors from growing and spreading in mice. The antibody therapy also boosted a type of T-cell-modifying immunotherapy in clinical use.

The researchers also show that this type of macrophage can be found in human breast cancer and malignant melanoma, and therefore hope to be able to develop an antibody that can one day be used for treating these patients.

“We now hope that this new therapy, which has so far been tested preclinically, will one day be used in combination with another immunotherapy to make it even more efficacious,” says Professor Karlsson. “We are also looking into whether the presence of this type of macrophage in human tumors can be used clinically for the diagnosis of cancer diseases.”

Anna-Maria Georgoudaki, Kajsa Prokopec, Vanessa F. Boura, Eva Hellqvist, Silke Sohn, Jeanette Östling, Rony Dahan, Robert A. Harris, Mattias Rantalainen, Daniel Klevebring, Malin Sund, Suzanne Egyhazi Brage, Jonas Fuxe, Charlotte Rolny, Fubin Li, Jeffrey V. Ravetch and Mikael C.I. Karlsson
Reprogramming tumor associated macrophages by antibody targeting inhibits cancer progression and metastasis
Cell Reports, May 2016 DOI: 10.1016/j.celrep.2016.04.084