Structures polymériques hydrophiles originales pour limiter l'hydrophobicité apparente d'anticorps armés (ADCs) afin d'optimiser leur index thérapeutique // New hydrophilic polymeric structures limiting the hydrophobicity of antibody-drug conjugate (ADCs)

Antibody-drug conjugates (ADCs) combine a very powerful cytotoxic agent with a monoclonal antibody (mAb) directed against an antigen overexpressed on the surface of cancer cells via a carefully designed chemical linker. Today, 19 ADCs (mAb-linker-cytotoxic) have been approved worldwide and successfully implemented in clinical strategies, while 200 clinical trials involving ADCs are in the recruitment phase or underway. However, despite the keen interest they have generated, most of the ADCs targeting solid tumors do not progress beyond phase 2 of clinical trials. In order to achieve greater translational success, one of the key parameters to optimize ADCs is the control of the hydrophobicity of the linker-cytotoxic. Indeed, hydrophobicity limits the number of cytotoxic agents that can be conjugated to an antibody without significantly degrading its pharmacokinetic and pharmacodynamic (PK-PD) properties. Furthermore, it contributes to ADC toxicity, promoting off-target uptake of the ADC within healthy cells that do not express the targeted antigen, particularly through the macropinocytosis process.
Thus, this inter- and multidisciplinary thesis project at the interface of chemistry/biology/material sciences, proposed by two complementary teams at the university of Tours (CEPR and PCM2E) aims to design and synthesize several families of hydrophilic polymers, acting as hydrophobicity controllers, to integrate them into the linker structures used to design ADCs. These hydrophilic polymers will then be grafted onto an original linker-cytotoxic, and these original molecular assemblies will then be conjugated to an antibody to produce different ADCs. The benefit provided by the hydrophilic polymers, in terms of apparent hydrophobicity of the ADCs, will be evaluated by HIC (hydrophobic interaction chromatography). The produced ADCs will then be tested in vitro and in vivo on non-small cell lung cancer (NSCLC) models.

For this project, the recruited PhD student will be working in PCM2E laboratory and will be in charge of the organic synthesis of the hydrophobicity control units for the linker-payload entities, which will then be conjugated to antibodies to produce the desired ADCs. The grafting onto the antibodies will be done in CEPR laboratory. Additionally to this working organization on two laboratories at Tours, the candidate will have the opportunity to participate in the in vitro tests at the Department of Pharmacy of the University of Salerno (Italy).
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Antibody-drug conjugates (ADCs) combine a very powerful cytotoxic agent with a monoclonal antibody (mAb) directed against an antigen overexpressed on the surface of cancer cells via a carefully designed chemical linker. Today, 19 ADCs (mAb-linker-cytotoxic) have been approved worldwide and successfully implemented in clinical strategies, while 200 clinical trials involving ADCs are in the recruitment phase or underway. However, despite the keen interest they have generated, most of the ADCs targeting solid tumors do not progress beyond phase 2 of clinical trials. In order to achieve greater translational success, one of the key parameters to optimize ADCs is the control of the hydrophobicity of the linker-cytotoxic. Indeed, hydrophobicity limits the number of cytotoxic agents that can be conjugated to an antibody without significantly degrading its pharmacokinetic and pharmacodynamic (PK-PD) properties. Furthermore, it contributes to ADC toxicity, promoting off-target uptake of the ADC within healthy cells that do not express the targeted antigen, particularly through the macropinocytosis process.
Thus, this inter- and multidisciplinary thesis project at the interface of chemistry/biology/material sciences, proposed by two complementary teams at the university of Tours (CEPR and PCM2E) aims to design and synthesize several families of hydrophilic polymers, acting as hydrophobicity controllers, to integrate them into the linker structures used to design ADCs. These hydrophilic polymers will then be grafted onto an original linker-cytotoxic, and these original molecular assemblies will then be conjugated to an antibody to produce different ADCs. The benefit provided by the hydrophilic polymers, in terms of apparent hydrophobicity of the ADCs, will be evaluated by HIC (hydrophobic interaction chromatography). The produced ADCs will then be tested in vitro and in vivo on non-small cell lung cancer (NSCLC) models.

For this project, the recruited PhD student will be working in PCM2E laboratory and will be in charge of the organic synthesis of the hydrophobicity control units for the linker-payload entities, which will then be conjugated to antibodies to produce the desired ADCs. The grafting onto the antibodies will be done in CEPR laboratory. Additionally to this working organization on two laboratories at Tours, the candidate will have the opportunity to participate in the in vitro tests at the Department of Pharmacy of the University of Salerno (Italy).
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Début de la thèse : 01/10/2026

Financement d'un établissement public Français

Université de Tours

552 Energie, Matériaux, Sciences de la Terre et de l'Univers - EMSTU

The candidate must have a MASTER 2 degree (BAC+5) and a good knowledge of organic chemistry. The candidate must be very motivated and able to make experiments with great care and reproducibility. The candidate must demonstrate a high degree of motivation for working in an interdisciplinary project, and master organic synthesis including purification techniques (flash chromatography and HPLC) and analytical techniques (especially HPLC) as well as good basis in polymer chemistry would be appreciated. A good command of English is also mandatory.
The candidate must have a MASTER 2 degree (BAC+5) and a good knowledge of organic chemistry. The candidate must be very motivated and able to make experiments with great care and reproducibility. The candidate must demonstrate a high degree of motivation for working in an interdisciplinary project, and master organic synthesis including purification techniques (flash chromatography and HPLC) and analytical techniques (especially HPLC) as well as good basis in polymer chemistry would be appreciated. A good command of English is also mandatory.