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Targeted Anti-Cancer Therapies

Periodic Reporting for period 1 - TACT (Targeted Anti-Cancer Therapies)

Reporting period: 2020-04-01 to 2022-03-31

According to the 2014 World Cancer Report, 8.2 million people died from cancer in 2012, 21.4% of whom being European citizens, whilst recent statistics reported 8.8 million deaths related to cancer in 2015. Despite marked improvements in outcomes for patients, 35% will still succumb to the disease, making cancer the second leading cause of death globally.
For the past years until now, chemotherapy has always been the way to go treatment against several cancers, accompanied by various adverse effects that were forcing the patient to endure pain for months or years.
Antibody-Drug Conjugates (ADCs) are fast growing classes of oncology therapeutics. ADC therapy targets the drug directly to the tumour reducing most of the side effects, though research in this field is still new and needs optimization. ADCs consist in a highly potent cytotoxic drug connected via a linker to an antibody that is specifically targeting certain tumour markers. By combining the cytotoxicity of the drug and the targeting properties of the antibody, ADCs kill cancer cells whilst leaving the healthy cells unaffected, thus broadening the effective therapeutic window of such therapies, a marked improvement compared to classical chemotherapies. Thus, after more than 50 years of research, the marketing of 4 ADCs – Adcetris™ (2011), Kadcyla® (2013), Besponsa™ (2017) and Mylotarg® (2017) – has provided clinicians with innovative therapeutics to fight metastatic breast cancer, Hodgkin and systemic anaplastic large cell lymphomas, as well as acute myelogenous and lymphoblastic leukemia. The approval of several new ADCs is hotly anticipated; as of October 2018, at least 83 candidates were in clinical trials.
Targeted Anti-Cancer Therapies (TACT) is an innovative, international, multidisciplinary training and research programme aiming to train 11 Early-Stage Researchers (ESRs) on the development of state-of-the-art targeted anti-cancer therapeutics and equip them with transferable, future career-enhancing skills to create the next generation of experts in Europe. More specifically, TACT’s research programme will focus on key interconnected priority themes for the conception of new and more effective generations of Protein-Drug Conjugates (PDCs): site-specific bioconjugation methods, more potent payloads, environment-specific cleavable linkers, more efficient protein-based targeting systems and new analytical tools for acute characterization. This will be achieved by exposing the ESRs to the leading intersectoral research scientists and laboratories in Europe who are active in this field. In doing so, TACT combines state-of-the-art research with excellent training in PDCs, one of the hot topics in cancer and targeted therapies.
As current PDC research and development activities are primarily located in North America, TACT also aims to create a European network for targeted therapies by building on 9 existing but isolated research groups and companies, dispersed over 5 European member states and associated countries, with expertise covering all research fields dealing with PDC. Finally, this training programme also intends to raise awareness of groundbreaking progress in the field of anti-cancer therapy among the non-scientific audience at a time of potential mistrust towards pharmaceutical research.
The work performed since the beginning of the project has been impeded by the sanitary situation and the flight restrictions in Europe. The beneficiaries showed a high level of flexibility and reacted quickly in order to keep the implementation pace. Thus, the project managed to start successfully in the middle of the lockdown.
The management structure (Work package 1) was set up since the beginning of the project, in particular the Supervisory Board which quickly led to negotiations over the Consortium agreement, finalised in month 6. The Executive Board was finalised with the swift recruitment of a European Project Manager. The other bodies such as the External Experts Advisory Board and the Gender Aspects Board were finalised in Year 2. The Supervisory Board is reactive and holds two meetings per year but also convenes exceptional meetings whever the situation requests for it.
One of the most important measure of flexibility was to decentralise the recruitment process in Year 1. In this perspective, the recruitment of the 11 foreseen PhD candidates happened as planned with each beneficiary initiating the procedure and holding the interviews. The beneficiary would then submit the final candidate's profile to the Coordinator and the arguments for his or her eligibility. Seven out of eleven ESRs are women. Most of the ESR started their positions in month 7, with two starting month 8 and the last one in month 10. The delays were due to visa issues or sanitary checks for overseas candidates. ESR 7 resigned from the project, but with the rapid reaction by the Coordinator and the beneficiary, another ESR will continue the project (selected in month 23 and due to start in month 26).
The network-wide meetings (Workpackage 2 and 7) also got implemented with a few changes in the timing and the format: the Coordinator proposed that the first training seminar be held on-line, which was confirmed by the organising partner and the Supervisory Board. The second networkwide meeting took place in a digital and on in-person form. The third meeting was finally held at the end of Year 2 as foreseen in the project proposal, during a full-week in-person with all the beneficiaries represented either by a fellow, or a fellow and PI and supervisor. In Work Package 2, the secondments have started in month 22 with a first wave of 5/11 ESRs in the move.
The communication strategy (Workshop 7) suffered also from the sanitary situation and the overwhelming presence of one sanitary topic. Howeve, with the right instruments developed by a professional studio and the first important scientific results expected in Year 3, the Executive Board feels confident that the topic of anti-body conjugates will find space for promotion and visibility.
As far as the scientific results are concerned, all partners have confirmed that the milestones proposed by the project have been reached, but one for which the beneficiary will propose a shift in the research, which. Nevertheless, the expected results have been reached with fliying colours and the remaining one are to be filanised in Year 3.
The Progress beyond state of the art is not visible at this point of implementation. The project is still in its infancy for impact to be measured, due to lack of high-profile results, which was expected at this stage of development though.
However, most of the beneficiaries have had significant scientific development in Year 2. The coming months promise concrete things: new campaign for Pink October and Movember 2, the forth and the fifth meeting at QUB with a training session about how to deal with patients, creation of the online space on Esperity, tutorial on the Youtube channel, progress of the graphical novel, creation of three films etc.
The long-term impact and wider societal implications are development of ADC with less side effects, better targeted ADCs and widespread of the methodologies to other types of cancers, as well as better awareness for a wider audience about their existence and visbility of targeted anti-caner therapies as a whole.
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