Young myelofibrosis patient Sarah Gardner* raised a large sum of money for MPN research. Thanks to her brilliant fundraising, the MPN AA was able to fund a fellowship for Dr Chloe Thompson-Peach at the South Australian Health and Medical Research Institute.
The research focuses on the CALR mutation and it is extremely promising.
Image: Dr Chloe Thompson-Peach from SAHMRI
Chloe’s report from the fellowship follows.
Lay Report by Dr. Chloe Thompson-Peach, fellowship recipient
Myelofibrosis is an insidious condition of the bone marrow, which disrupts the normal production of blood cells. It is characterised by painful inflammation, low blood counts and fibrous tissue building up in the bone marrow. In some patients, myelofibrosis can also develop into acute leukaemia over time. The lack of effective therapeutic options for these cancers has led us to the development of a new immune treatment for these individuals.
We have developed a novel immune treatment, a biological therapy, that is a monoclonal antibody directed against the mutant CALR gene, which is the second most common cause of myelofibrosis or essential thrombocythemia.
We have shown this to be effective in cell lines and patient cells harbouring pathogenic CALR mutations in the laboratory.
Additionally, our treatment has also been shown to have no effect on cell lines and patient cells that do not carry mutations within the CALR gene, suggesting it is truly selective, which means it will not have side effects.
This was published recently in a major European science journal, EMBO Reports.
EXCITING UPDATE:
We have recently developed a new version of our antibody which is able to be used in humans without being rejected (called antibody humanisation) and demonstrated that the antibody is still effective at eliminating mutant CALR cells, while leaving healthy normal cells unharmed. We have shown that our antibody is able to significantly reduce the live burden of disease, with mutant cells being completely eradicated in pre-clinical in vivo experiments.
Our antibody reduced the number and size of megakaryocytes formed in CALR mutant patient samples in the lab, a key cell in driving myelofibrosis.
Additionally, we have shown that this antibody can be combined with Jakafi (ruxolitinib) to completely eradicate mutant CALR cells in the lab and re-sensitise cells that are resistant to ruxolitinib therapy alone.
Importantly, our human antibody has shown no signs of toxicity in mice and is in the process of preparation for clinical trial in the near future.
The good news is we have worked out which parts of the mutant CALR protein that causes myelofibrosis can be blocked by the antibody and it looks like we have another antibody that also has activity. We are now using the molecular information we have gained from these antibodies to build new cell therapies (CAR T cell or NK therapies or “bispecific T cell engager” antibodies).
We are hopeful that our research can build a suite of therapies, either to be used on their own or in combination with Jakafi, that will be effective and help move towards demonstration of long-term remission or cure in patients with myelofibrosis, as well as in patients that relapse after a stem cell transplant.
Some of our data was presented at the recent “New Directions in Leukaemia” conference organised by my supervisor Dr Dan Thomas at the University of Adelaide and Stanford University and is under review at a major international journal.
Please stay tuned and thank you for being committed to changing outcomes for patients with MPNs!
*Sarah Gardner’s story is available HERE.
