Application of protein-drug conjugates for the treatment of cancer (part of the ETN Targeted Anti-Cancer Therapies “TACT”)

Macromolecular drug substances such as antibodies, ADCs and nanomedicine are often compromised in their therapeutic effectiveness due to inability to penetrate sufficiently into the diseased tissue and be taken up by the diseased cells. This is particularly apparent in pancreatic cancer and some forms of colorectal cancer, characterized by a stromal rich microenvironment, which essentially acts as a wall to drug deposition. We hypothesize that active antibody targeting and compromisation of this desmoplasia using agents such as sonic hedgehog inhibitors or Fasudil (both which abrogate fibroblast interactions by different mechanisms) may improve the efficacy of ADCs, nanomedicines and targeted nanomedicines. Therefore, the overall aim of this project will be to develop and evaluate PDCs or antibody targeted nanoconjugates that will bind to tumor-associated antigens in cancer (e.g. EGFR). These drugs will be evaluated in models of cancer to determine their therapeutic effect and if other agents (e.g. Fasudil) improve targeting and distribution in hard to treat tumors.

Expected Results: anticipated results from this research will include the development of novel antibody targeted nanoconjugates and PDCs. These will then be evaluated in models of cancer, both in-vitro and in-vivo, to determine therapeutic effects, as well as understand possible toxicities and potential to improve biodistribution through tumor priming. Planned secondment(s): CNRS, S. Cianferani, month 25, 3 months: characterization of new mAb format by mass spectrometry / SPC, T. Fessard, month 34, 3 months: synthesis of Fasudil bioisostere analogues.

Project. ‘Targeted Anti-Cancer Therapies’ (TACT) is a ‘European Training Network’ (ETN) research project that received funding by the European Commission under the ‘Horizon 2020 research and innovation programme’ and the ‘Marie Skłodowska-Curie actions’. Being an international and multidisciplinary training and research doctoral programme, TACT aims 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. 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, more efficient protein-based targeting systems and new analytical tools for acute characterization.

This will be made possible thanks to a unique cooperation between academic and industrial worlds, resulting in a consortium comprising nine beneficiary institutions: University of Strasbourg and CNRS (France); University College of London, Queen’s University of Belfast and Almac Discovery (U. K.); Technical University of Munich and Heidelberg Pharma (Germany); University of Waggeningen (Netherlands); Spirochem AG (Switzerland). Each of these institutions will host and train at least one ESR, who will benefit from an unequalled scientific training in all domains related to the field of PDCs via their main research projects, secondments at other institutions and network-wide meetings.

Applications. The TACT consortium is looking for highly talented, motivated and qualified graduate students in various fields at the interface of chemistry, biology and analytical chemistry to start October, 1st 2020. The candidates will have to possess a strong interest in interdisciplinary research and be willing to take part in various communication activities towards non-scientific public. They will have to be fluent in English, possess a high degree of self-organisation and be able to work collaboratively. Applicants can visit www.tact-etn.eu to visualize the different research projects proposed in this programme.

ENTRY REQUIREMENTS
Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language
Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.
For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English