Pbox-15, a potential new drug compound discovered by Irish clinical scientists, is found to be highly powerful against cancers including the toughest drug-resistant chronic lymphocytic leukaemia.
Pbox-15, which has been singled out from 75 related compounds belonging to a new class of drugs, works better than the drugs currently in use but also seems to leave healthy tissues untouched.
Pbox-15 was tested in cancer cells actually recovered from patients rather than standard cancer cell lines.
The cells were taken with consent from 55 chronic lymphocytic leukaemia (CLL) patients, including those who had not responded well to the main drug currently used against the disease, fludarabine.
Pbox-15 was found to be having a very strong effect. Pbox-15 readily killed leukaemia cells, including those taken from patients who had shown resistance to therapies already in use.
“It did that better than the drugs we normally use to treat leukaemia,” stated Prof Mark Lawler of Trinity College Dublin and St James’s Hospital, who led the team.
Pbox-15 was able to kill the cells without harming healthy blood and bone marrow cells.
Researchers now plans to test Pbox-15 against chronic lymphocytic leukaemia (CLL), the most common leukaemia in the western world. Chronic lymphocytic leukaemia can sometimes be resistant to current treatments.
The drug seems to be able to trigger “apoptosis” or natural cell death in cancer cells, Prof Lawler said. This is important given cancer cells effectively forget how to die and begin to grow out of control.
Pbox-15, however, did not harm normal blood or bone marrow cells. Hence, researchers would like to believe that Pbox-15 targets cell death pathways that are only present in the leukaemia cells and not in normal tissues.
Pbox-15 findings “emphasise the potential for basic science discoveries to translate to clinical benefit”, stated the Irish Cancer Society. These findings needed to be brought as quickly as possible “from the laboratory to the bedside, so that they will ultimately benefit patients with this common form of leukaemia”.
Irish Cancer Society was the main funder of the study. The research group also received funding from Science Foundation Ireland, Enterprise Ireland and the HEA’s Programme for Research in third-level institutions.
The researchers included Trinity academics and researchers in Belfast City Hospital and the University of Siena, Italy, involved in chemistry, biochemistry and molecular medicine.
It could take another three to five years before Pbox-15 could be used in human trials, researchers said.
Chronic lymphoid leukemia, CLL is a monoclonal disorder characterized by a progressive accumulation of functionally incompetent lymphocytes. It is the most common form of leukemia found in adults in Western countries.
The cells of origin in the majority of patients with chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL) are clonal B cells arrested in the B-cell differentiation pathway, intermediate between pre-B cells and mature B cells. Morphologically in the peripheral blood, these cells resemble mature lymphocytes.
B-cell chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL) lymphocytes typically show B-cell surface antigens, as demonstrated by CD19, CD20, CD21, and CD23 monoclonal antibodies. In addition, they express CD5, which is more typically found on T cells.
The signs and symptoms of CLL can include the following:
* Frequent infections, as people with CLL have a shortage of healthy white blood cells to produce antibodies and fight off bacteria and viruses.
* A lack of red blood cells (anaemia) causes tiredness and sometimes breathlessness. There are not enough red blood cells because the abnormal lymphocytes are taking up too much space in the bone marrow. Sometimes the numbers of red blood cells may be low because the leukaemia causes particular proteins to be produced that damage the red blood cells.
* The number of platelets in your blood may be low because the bone marrow is not able to produce enough of them. This can cause unexplained bruising or bleeding, such as nosebleeds.
* Abnormal lymphocytes may collect in lymph glands and cause swellings in your neck, armpits or groin. The swollen lymph glands are usually painless but may be sore. Your spleen may become enlarged and cause a tender lump in the upper left-hand side of your abdomen.
* Some people will have sweating or a high temperature at night can also sometimes occur.
* Some people will lose weight.