Engineered white blood cells may eliminate cancer?

By silencing the molecular pathway that prevents macrophages from attacking our own cells, University of Pennsylvania engineers have manipulated these white blood cells to eliminate solid tumors.

https://medicalxpress.com/news/2023-06-white-blood-cells-cancer.html

Cancers that form solid tumors such as in the breast, brain, or skin are particularly hard to treat. Surgery is typically the first line of defense for patients fighting solid tumors. But surgery may not remove all cancerous cells, and leftover cells can mutate and spread throughout the body. A more targeted and wholistic treatment could replace the blunt approach of surgery with one that eliminates cancer from the inside using our own cells.

The challenge is to find a way for our own macrophages to recognize cancer cells, i.e., discern cancer cells from healthy cells.

Macrophages, a type of white blood cell, immediately engulf and destroy—phagocytize—invaders such as bacteria, viruses, and even implants to remove them from the body. A macrophage's innate immune response teaches our bodies to remember and attack invading cells in the future. This learned immunity is essential to creating a kind of cancer vaccine.

But, a macrophage can't attack what it can't see.

"Macrophages recognize cancer cells as part of the body, not invaders," says Dooling. "To allow these white blood cells to see and attack cancer cells, we had to investigate the molecular pathway that controls cell-to-cell communication. Turning off this pathway—a checkpoint interaction between a protein called SIRPa on the macrophage and the CD47 protein found on all 'self' cells—was the key to creating this therapy."

https://www.nature.com/articles/s41551-023-01031-3 (Subscription or purchase required)

Generally, our immune system does recognise abnormal cells and for cancers to develop a range of mutations have to occur, one of which must protect the abnormal cells from being recognised and destroyed. There are an increasing number of the so-called biologic drugs which specifically target the molecular messengers that help protect the cancer cells. These can be combined with techniques to improve the recognition of the malignant cells, even at the level of a specific individual's cancer. There are unfortunately, a number of issue effecting the interactions between solid tumours and the immune system, a solid tumour characteristically will have areas of hypoxia containing dead or dormant cells and many of these cells will contain a variety of mutations which may potentially protect them.

People often consider our immune system to be a benign force to protect us, unfortunately it is far from benign, it requires careful control to prevent it attacking normal tissues, many of these drugs have their effect because they remove this control. So while these drug's are generally safer than traditional chemotherapy, they are still associated with significant risks.

Causing the death of a large number of malignant cells using drugs or radiation, does in itself activate the immune system and allows the immune system to recognise tumour cells. This effect becomes more powerful when combined with various biologic drugs that block some of the control molecules. The techniques described in the article describe the development of techniques based on vaccine technology, which represents further developments in fine tuning the immune responses and making them more specific.

A number of different approaches are already available but the cost of such individual approaches limits their use and solid tumours present a particular challenge. There is a lot of money going into cancer therapeutics and in some ways the pace of developments is staggering, perhaps the so called moon-shot in cancer research is paying off.