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Targeting bone disease in myeloma

Multiple myeloma is a cancer of the blood, but as it progresses the blood cancer cells collect in the bone marrow, the spongy centre of bones like the spine, pelvis and ribs.  Here they release molecules that cause bone to be broken down, weakening it, causing pain and eventually the bone to fracture and collapse.  The damage caused by myeloma cells inside bones is known as myeloma bone disease and it is the most debilitating symptom of this type of cancer.  Almost all patients with myeloma get bone damage and all are put on treatments to try to contain it.Current treatments for myeloma bone disease can slow it down, but they cannot stop it. 

Dr Goodyear will use his Worldwide Cancer Research grant to investigate what he thinks could be a new way of preventing myeloma cells from causing bone damage.  His laboratory has discovered a type of antibody complex, called SIC, that is able to dock onto the surface of the bone-damaging cells and quench their activity.  He will test this potential new treatment in a mouse model of myeloma, and investigate whether it might also help stop the myeloma itself as well as control the bone damage.

If successful, this line of research might not only lead to a new treatment for myeloma, it could also be important for other cancers that often spread to the bone, like breast and prostate cancer.

Developing new treatments for multiple myeloma (MM)

Dr. Hans van der Vliet is using his Worldwide Cancer Research grant to develop a new treatment for multiple myeloma (MM). MM develops from cells in the bone marrow called plasma cells. Normally, new plasma cells are produced to replace old, worn-out cells in an orderly, controlled way. However, in myeloma, the process gets out of control and large numbers of abnormal plasma cells (myeloma cells) are produced. These fill up the bone marrow and interfere with the production of normal white blood cells, red blood cells and platelets which causes many problems for the patient.

Dr van der Vliet is developing a new biological treatment against MM using parts of antibodies. These special antibodies act upon a protein called CD1d which is found at much higher levels on MM and triggering of CD1d has already been shown to kill MM cells in lab based tests. Another way to kill MM cells is by activating immune system cells designed to kill foreign bodies, with the catchy name gamma-delta T cells. Dr van der Vliet plans to combine both of these approaches to create an even more potent treatment which will first be tested in the lab and then in mice as no other methods can be used.

Dr Hans van der Vliet hopes that if successful, his new treatment could enter clinical trials in patients. He believes it could not only benefit patients with MM but potentially also people with chronic lymphocytic leukaemia (CLL), lymphomas, certain gliomas, breast, lung, prostate and bowel cancers which all have high levels of CD1d.

Making sure bone marrow cancer cells have nowhere to hide

Working in the Netherlands, Dr Tuna Mutis has recently made progress in understanding why multiple myeloma cells can sometimes become resistant to immune therapy. Using a new grant from Worldwide Cancer Research, he is now investigating in mice if combining immune therapy with agents that block these resistance mechanisms might improve treatment success.

Immune therapy is one of the most promising treatments for multiple myeloma. ‘Killer’ T cells from a healthy bone marrow donor are used to attack the myeloma cells in the patient’s bone marrow. But sometimes the cancer cells can become resistant and escape from the clutches of the killer cells.

In earlier lab studies Dr Mutis has found that the cancer cells can use their connections with surrounding cells in the bone marrow to protect themselves from killer T cells. He has also shown that this mechanism can be disrupted by a small molecule, called YM155. With his new grant he will build on these exciting findings by studying and modulating these mechanisms in greater depth in a new mouse model of the disease. If successful, this research could ultimately lead to vastly improved treatments for patients with multiple myeloma.