Members Area COST Action number CA17138

STSM Report: Nathaniel Saidu

How molecular biology and pharmacogenetics can help to understand the immune system’s behavior during the treatment of cGVHD with immunotherapy: the role of PD-L1, Torquetenovirus and of the assessment of tyrosine kinase inhibitors plasma levels.

STSM title: How molecular biology and pharmacogenetics can help to understand the immune system’s behavior during the treatment of cGVHD with immunotherapy: the role of PD-L1, Torquetenovirus and of the assessment of tyrosine kinase inhibitors plasma levels.

My name is Nathaniel Edward Bennett Saidu and my short term scientific mission was within Working Group 5, which is a working group on immunotherapy for the treatment of cGvHD. The aim of this mission was to gain an insight into existing immunotherapeutic strategies for the treatment of cGvHD via a) the retrieval and review of literature, b) setting of PCR for evaluating not only PDL-1 SNPs that could be relevant in cGvHD onset and response to immunotherapy, but also in different hematological conditions treated with tyrosine kinase inhibitors (such as in chronic myeloid leukaemia) and c) the evaluation of Torquetenovirus load pre- and after-allogeneic transplantation (analysis of data already available on patients treated in Pisa); all under the supervision of Prof. Sara Galimberti who is an expert in cancer immunotherapy at the Haematology Department of the University Hospital in Pisa, Italy.

During my time in Pisa, I have been able to draw a broad outline for a review paper on immunotherapy for cGvHD and I am currently in the process of writing this paper; all based on the extensive literature review that I did on immunotherapy for the treatment of cGvHD in both pre-clinical (animal and in vitro) and clinical (human) models.

This STSM has reinforced cooperation between COST member institutions within the COST action. I was also able to present at the last COST Action Meeting in Pisa, 6-7.02.2019, the outcomes of this STSM, where I shared my experiences from the STSM and made recommendations for future STSMs.

The STSM relates to Grant Action Period Goal 2, ‘Review the literature from the past 10 years on immunotherapeutic challenges for the treatment of cGvHD resistant to conventional therapy’. The STSM also relates to objectives of other work groups. All of these were accomplished from my STSM and hence, contributes to the scientific aims of the COST action.

I also gained an insight into the use of HPLC to measure plasma drug concentrations and Digital droplet PCR for mutational analysis. From analysing data on patients who underwent allogeneic bone marrow transplantation at the haematology unit, University Hospital, Pisa, I was able to differentiate between those that developed acute and chronic GvHD, including their outcome and toxicities after treatment with anti-TGF, anti-CD26 or TKIs, and those that didn’t. Reviewing literature on new treatments for resistant cases for some of these patients gave me a better understanding of the newer strategies that are out there for the treatment of some of these diseases.

As a result of this STSM, collaboration amongst several COST member institutions (University hospitals in Pisa, Italy; Zagreb, Crotia; and Warsaw, Poland) has been strengthened. These COST member insitutions have decided to come together to address ‘single-nucleotide polymorphisms (SNPs)‘ for predicting the sensitivity to newer drugs via sharing ethically approved clinical results from leukeamia and/cGvHD patients receiving TKIs at the respective member hospitals. This will then enable member insitutions to look at, evaluate and compare the pharmacokinetics of TKIs in these patients from various hospitals. They can also each assess the possible pharmacogenetic factors that may or may not influence the kinetics of TKIs. Furthermore, it will enable the analysis of population pharmacokinetics for the identification of possible factors that might influence the kinetics of BCR-Abl TKI in leukaemia and/or cGVHD. Hence, enabling the  therapeutic drug monitoring of TKIs in these diseases.

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