Vicky F
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A new wave of targeted leukaemia therapies could revolutionise treatment

Vicky F
Posted by
28 May 2015
Conventional treatments for most leukaemias involve a cocktail of chemotherapy drugs.  Most of these can be considered 'non-specific,' meaning that as well as killing the leukaemia cells, they unfortunately target normal, healthy cells too, as anyone who has ever lost their hair during treatment will know. 


Some chemotherapy drugs are more likely to affect fast-dividing cells, meaning that the uncontrollably dividing leukaemia blast cells are targeted, but also cells such as those in the stomach lining, resulting in many people on treatment experiencing nausea and sickness.

Some children experience severe neurological side effects from the treatment (although thankfully this is rare), like me twenty years ago.  When on treatment, I had something called stroke-like syndrome, meaning I was temporarily paralysed down my left hand side, which was terrifying for myself and my family. The numerous unpleasant side effects of chemotherapy treatment are why we need to strive towards developing therapies which only target leukaemia cells. 

The first ever targeted therapy, called imatinib was approved in 2001 for the treatment of chronic myeloid leukaemia (CML).  It targets the BCR-ABL translocation, an abnormal fusion between two pieces of DNA (also referred to as the Philadelphia Chromosome), which is found in CML and some cases of ALL.  I did a TED talk last year on the development of the drug and the inspiring scientist Dr Janet Rowley, who discovered BCR-ABL and paved the way for imatinib and thousands of lives saved.  Some people might argue, that the success of imatinib has not been built on quickly enough, but finally a new wave of exciting, targeted treatments for leukaemia known as chimeric antigen receptor (CAR) T-cell therapies are showing early promise in clinical trials.

One exciting CAR treatment targeting a protein called CD19 has been gaining a lot of interest in the medical community and has successfully achieved remission in a high percentage of both children and adults with ALL in recent clinical trials, including 91% of 33 adults in an new study presented this weekend at a major cancer conference.  Unlike BCR-ABL, CD19 is a normal protein, found on the surface of a certain type of white blood cell called a B-cell.  Normally these B-cells help to fight infection in a number of ways, including producing antibodies and releasing chemicals called cytokines, which help call the rest of the immune system to action against foreign invaders such as bacteria. However in B-cell leukaemias, abnormal quantities of these not fully developed B cells fill the blood and bone marrow to the exclusion of healthy blood cells.



Cells contain combinations of thousands of different proteins that make them unique and suitable for a wide range of different functions in our bodies, and lots of CD19 molecules are amongst many variable proteins stuck on the surface of B-cells. Scientists have been able to genetically engineer another type of white blood cell, a T-cell, which is taken from a patient and then changed slightly to make it attack CD19. The cells are transplanted back into the patient, and they then proceed to attack the B-cells, but only the B-cells as they are the only ones with CD19. Healthy B-cells are also unfortunately attacked by the treatment, but most other types or blood cells are unaffected. Normal conventional chemotherapy treatments can’t discriminate in this way.

This means that as the leukaemia cells are cleared from the system, other types of immune cell called myeloid cells and other blood cell types like platelets can recover as the targeted drug won't affect them. Under normal chemotherapy treatment, these healthy cells struggle to recover as they're similarly affected by the chemo. This is part of the reason why leukaemia patients have so many transfusions of red blood cells, platelets etc and are often neutropenic and vulnerable to infection. With targeted treatments, cells that aren't affected by leukaemia would be left alone.

Additionally, healthy cells from elsewhere in the body such as nerves, the digestive system and hair follicles aren’t affected, as the engineered T-cells simply can't stick to them to coordinate an attack.  Although engineered T-cells are in an early stage of development and lots more work needs to be done to investigate them fully, its possible that the T-cells can be designed to attack lots of different surface proteins, targeting not only different types of leukaemia, but other cancers too.

Recently there has been a dramatic change in focus towards inventing and testing these targeted drugs with fewer associated side effects than conventional chemotherapies.  Treatment regimens for some types of childhood leukaemia now have a 90% success rate, however its reassuring that these old drugs, which cause a host of unpleasant side effects could now potentially be gradually replaced with effective, yet kinder treatments.


With thanks to Judith Weiland, RWTH Aachen University Medical Centre, Germany/Newcastle University, UK for co-writing this blog based on her publication:

'CD19: A multifunctional immunological target molecule and its implications for Blineage acute lymphoblastic leukemia.' Judith Weiland, Alex Elder, Victoria Forster, Olaf Heidenreich, Steffen Koschmieder and Josef Vormoor. Pediatric Blood and Cancer, 2015.

Photo credit: AACR




This all sounds fantastic! Thank you so, so much for everything that you're doing to try and find ways to make treatments less toxic and harmful for patients. The short term and long-term side effects of treatment have been overlooked in the past but are now coming more into focus as more patients survive the initial treatment.

As one of those lucky patients to have survived initial treatment but suffered long-term side effects in recent years, I'm very passionate about this field of research and really admire everything that you're doing. Keep at it and thanks so much for looking to make a better future for blood cancer patients. You are genuinely one of my heroes!


A brilliant article, Vicky. I had heard and knew a tiny modicum about CAR T cells and how they work but your explanation is so clear and relatively simple - a rare skill to be able to communicate so clearly.

Our younger son, Tim, died of ALL, in 2005, at the age of 23 and we are dedicated to doing what we can to make sure that every patient with blood cancer gets the opportunity to make their dreams come true. The work you and your fantastic colleagues are doing is changing the world and your role as a leukaemia Survivor is especially important.
THANK YOU and take care.