RIT: an exciting new treatment for acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a blood-borne cancer that has responded extremely well to radioimmunotherapy in clinical and non-clinical trials. Most studies targeted the protein CD33 which is found in high amounts on the surface of most AML cells. The antibody, M195, recognises and binds to CD33. In a research study, M195 was joined to a radioactive agent and used to treat AML patients. Within one hour of administration, the radioactively labelled antibodies had found and bound to the leukaemia cells, showing an extremely powerful anti-cancer effect as more than 99% of the leukaemia cells were killed.

Usually, the only hope for patients with recurrent or unresponsive (to chemotherapy) leukaemias is an allogeneic bone marrow transplant (BMT), involving bone marrow cells being taken from a donor and transplanted into the patient; however, this only results in a 20-25% cure rate. In an attempt to increase the cure rate, scientists have tested the effects of adding radioactive antibodies to the normal pre-transplant treatment routine; usually involving chemotherapy drugs. The reason cancer treatments are given before a bone marrow transplant is to kill as many of the cancerous blood cells as possible before the new, healthy blood cells are transplanted into the patient, this reduces the risk of the cancer returning. One study produced outstanding cure rates of 93% following the bone marrow transplant.

For more information on bone marrow transplants visit the National Cancer Institute:
http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant

RIT before a bone marrow transplant in advanced acute leukaemia patients

The best chance of curing a patient with advanced acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS); both being types of blood cancer, is with a bone marrow transplant, although the number of long term survivors after transplant is on average only 30% for both diseases. The high doses of external radiation and chemotherapy usually used to kill leukaemia cells before new, healthy blood cells are transplanted; cause severe side effects, as they damage a lot of normal, healthy cells too. Also, although these cancer treatments are high dose, in many patients who have received a bone marrow transplant, the cancer returns. To reduce the risk of the cancer returning, researchers have investigated using radioimmunotherapy (RIT) to deliver targeted radiation to diseased blood cells, killing them, before receiving new transplanted blood cells. The chosen target was the protein CD45, which is found on most blood cell surfaces. Research has shown that using an antibody recognising the CD45 surface protein was attached to a radioactive molecule, in patients with acute leukaemia, more than 5 times more radiation was delivered to the tissues that make new blood cells, like the bone marrow and spleen, compared to any other organ. This shows how RIT has the ability to deliver very high amounts of radiation that can be targeted to sites of disease, due to the combination of specific antibody and cell damaging effects of radiation, which could potentially reduce the risk of the cancer returning.

For more information see the Fred Hutchinson Cancer Research Centre: http://www.fhcrc.org/

An Overview of Radioimmunotherapy

Despite the success of current cancer treatments such as chemotherapy, serious damage to normal cells and organs occurs, which severe side effects and possibly even a risk of developing a second cancer. Therefore, there is still a need for an improved therapy for cancers; one which is proving extremely promising is radioimmunotherapy (RIT). This technique involves a protein, called an antibody, being labelled with a radioactive molecule. When administered to the patient, the radioactive antibody travels around the body until it recognises and binds to certain protein ‘markers’ present on the surface of the cancer cells, as illustrated in the diagram. Antibodies are known for their selectivity, and in RIT, they enable selective targeting of cancer cells, and specific delivery of the radioactive molecule to the tumour site. Once the radioactive antibody is attached to the cell, the radioactive molecule releases its radiation directly onto the tumour cell, damaging the cells DNA and killing the cell. As radiation can only travel so far, normal cells in the surrounding area receive minimal amounts of radiation. This blog was created to make cancer patients and their families aware of this new and exciting cancer treatment, and give examples of trials involving RIT, as well as results obtained.

A new approach in treating acute myeloid leukaemia; directing radiation into the cancer cell

Acute myeloid leukaemias (AML) account for 40% of all adult leukaemias, with the number of patients being diagnosed rapidly, especially in the elderly. Although current treatments, such as chemotherapy, cures 60-80% of AML patients, in most cases the cancer comes back. Once the cancer has returned, it is a lot more difficult to treat, with the cure rate after patients have received chemotherapy to treat the returning cancer, dropping dramatically to only 10-15%. The growing numbers of AML patients and the ineffectiveness of current treatment, means there is a desperate need for an alternative, more effective therapy for AML patients. One such therapy is radioimmunotherapy (RIT), which is a powerful new approach in selectively targeting and killing cancer cells, yet avoiding normal cells. Research involving RIT for patients with returning AML, have targeted the CD33 protein, present on the surface of most blood cells.
CD33 is specifically targeted by the antibody M195, which was attached to a variety of radioactive molecules that all released different types of radiation. Results showing an excellent cancer killing ability, however, most also damaged normal tissue in the direct vicinity of the tumour, due the relatively long distances travelled by the type of radiation used. Although this normal tissue damage was no where near the levels of damage caused by chemotherapy, it was still far from ideal. In an attempt to reduce this normal cell damage a different radioactive molecule; releasing radiation that could only travel very short distances, was attached to M195. As the radiation only travels short distances, it is only harmful to a cell if it is actually inside it. A special technique was used to direct this radioactive antibody into the cancer cell; once inside the radiation caused serious DNA damage, killing the cell. The surrounding cells were left completely unharmed.

RIT: an exciting new treatment for acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a blood-borne cancer that has responded extremely well to radioimmunotherapy in trials. Most studies targeted the protein CD33 which is found in high numbers on the surface of most AML cells. The antibody M195 recognises and binds to CD33. In a research study, M195 was joined to a radioactive agent and used to treat AML patients. Within one hour of administration, the radioactively labelled antibodies had found and bound to the leukaemia cells, showing an extremely powerful anti-cancer effect with the death of more than 99% of the leukaemia cells.
Usually, an allogeneic bone marrow transplant (BMT), involving bone marrow cells being taken from a donor and transplanted into the patient, is the only chance for a cure for patients with returning or unresponsive (to chemotherapy) leukaemias. Although, even this treatment results in only a 20-25% cure rate. Scientists decided to use radioactive antibodies in an attempt to increase the number of leukaemia patients being cured. Experiments including radioactive antibodies into the normal treatment routine with the usual cancer therapies; chemotherapy drugs and/or radiation treatment of the entire body. The reason cancer treatments are used before a bone marrow transplant is to kill as many of the cancerous blood cells as possible before the new, healthy blood cells are transplanted into the patient, therefore lowering the risk that the cancer will return. The outstanding results showed a cure rate of 93% following the bone marrow transplant.

For further information:
http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant