Le laboratoire se focalise sur le développement de nouveaux médicaments thérapeutiques contre le cancer, leur conjugaison sur des plateformes de délivrances ciblées (anticorps, nanoparticules), et la conception de nouveaux ligands permettant une délivrance contrôlée améliorée.

Projets

Nanomédecine et myélome multiple

2023 - Porteur du projet : Dr DETAPPE Alexandre

Brush-arm Antibody Drug Conjugate as theranostic approach for ovarian cancer

2020 - Porteur du projet : Dr DETAPPE Alexandre - Partenaires : Dr CHARBONNIERE Loïc, Dr GOETZ Jacky

Publications

Landscape of Subcutaneous Administration Strategies for Monoclonal Antibodies in Oncology.

Jacquot G, Lopez Navarro P, Grange C, Boudali L, Harlepp S, Pivot X, Detappe A

Adv Mater. 2024 08 20;:e2406604

Chemical Production of Cytotoxic Bispecific Antibodies Using the Ugi Multicomponent Reaction.

Vaur V, Koutsopetras I, Erb S, Jackowska B, Benazza R, Cahuzac H, Detappe A, Hernandez-Alba O, Cianférani S, Scott CJ, Chaubet G

Chembiochem. 2024 05 7;:e202400170

Supramolecular Heterodimer Peptides Assembly for Nanoparticles Functionalization.

Mathieu C, Ghosh S, Draussin J, Gasser A, Jacquot G, Banerjee M, Gupta T, Schmutz M, Mirjolet C, Tillement O, Lux F, Klymchenko A, Donzeau M, Pivot X, Harlepp S, Detappe A

Adv Healthc Mater. 2024 03 5;:e2304250

Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies.

Gréa T, Jacquot G, Durand A, Mathieu C, Gasser A, Zhu C, Banerjee M, Hucteau E, Mallard J, Lopez Navarro P, Popescu BV, Thomas E, Kryza D, Sidi-Boumedine J, Ferrauto G, Gianolio E, Fleith G, Combet J, Brun S, Erb S, Cianferani S, Charbonnière LJ, Fellmann L, Mirjolet C, David L, Tillement O, Lux F, Harlepp S, Pivot X, Detappe A

Adv Mater. 2023 12 17;:e2308738

Influence of pneumatic transportation on the stability of monoclonal antibodies.

Coliat P, Erb S, Diemer H, Karouby D, Martin T, Banerjee M, Zhu C, Demarchi M, Cianférani S, Detappe A, Pivot X

Sci Rep. 2023 12 10;13(1):21875

Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction.

Koutsopetras I, Vaur V, Benazza R, Diemer H, Sornay C, Ersoy Y, Rochet L, Longo C, Hernandez-Alba O, Erb S, Detappe A, Skerra A, Wagner A, Cianferani S, Chaubet G

Chemistry. 2023 12 5;:e202303242

An autoinhibited state of 53BP1 revealed by small molecule antagonists and protein engineering.

Cui G, Botuyan MV, Drané P, Hu Q, Bragantini B, Thompson JR, Schuller DJ, Detappe A, Perfetti MT, James LI, Frye SV, Chowdhury D, Mer G

Nat Commun. 2023 09 29;14(1):6091

Molecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma.

Detappe A, Nguyen HV, Jiang Y, Agius MP, Wang W, Mathieu C, Su NK, Kristufek SL, Lundberg DJ, Bhagchandani S, Ghobrial IM, Ghoroghchian PP, Johnson JA

Nat Nanotechnol. 2023 01 26;:

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects.

Diringer MC, Coliat P, Mathieu C, Laurent N, Mura C, Banerjee M, Zhu C, Grabowska A, Ritchie A, Clarke P, Bernard A, Vit C, Burckel H, Noel G, Harvey P, Pivot X, Detappe A

Small. 2023 01 1;:e2205961

A Combination of Native LC-MS Approaches for the Comprehensive Characterization of the Antibody-Drug Conjugate Trastuzumab Deruxtecan.

Deslignière E, Diemer H, Erb S, Coliat P, Pivot X, Detappe A, Hernandez-Alba O, Cianférani S

Front Biosci (Landmark Ed). 2022 10 26;27(10):290

Optimal Physicochemical Properties of Antibody-Nanoparticle Conjugates for Improved Tumor Targeting.

Mittelheisser V, Coliat P, Moeglin E, Goepp L, Goetz JG, Charbonnière LJ, Pivot X, Detappe A

Adv Mater. 2022 Mar 15;:e2110305

Anti-BCMA Immuno-nanoPET Radiotracers for Improved Detection of Multiple Myeloma.

Thomas E, Mathieu C, Moreno-Gaona P, Mittelheisser V, Lux F, Tillement O, Pivot X, Ghoroghchian PP, Detappe A

Adv Healthc Mater. 2021 Oct 28;:e2101565

TROIKA-1: A double-blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU-Herceptin and US-Herceptin in healthy male subjects.

Demarchi M, Coliat P, Mclendon K, Chung Shii Hii J, Feyaerts P, Ang F, Jaison L, Deforce F, Derde MP, Kim MJ, Park LS, Detappe A, Pivot X

Pharmacol Res Perspect. 2021 Aug;9(4):e00839

Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation.

Mertes PM, Collange O, Coliat P, Banerjee M, Diringer MC, Roche A, Delabranche X, Chaban V, Voegelin M, Bernard A, Sartori V, Laurent N, Velten M, Dhindsa N, Defuria J, Kim G, Xu ZH, Theodorou M, Huang ZR, Khalifa K, Geng B, Niyikiza C, Moyo V, Gizzi P, Villa P, Detappe A, Pivot X

J Control Release. 2021 Jun 24;:

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes.

Ghoroghi S, Mary B, Larnicol A, Asokan N, Klein A, Osmani N, Busnelli I, Delalande F, Paul N, Halary S, Gros F, Fouillen L, Haeberle AM, Royer C, Spiegelhalter C, André-Grégoire G, Mittelheisser V, Detappe A, Murphy K, Timpson P, Carapito R, Blot-Chabaud M, Gavard J, Carapito C, Vitale N, Lefebvre O, Goetz JG, Hyenne V

Elife. 2021 Jan 6;10:

Pro-organic radical contrast agents ("pro-ORCAs") for real-time MRI of pro-drug activation in biological systems.

Nguyen HV, Detappe A, Harvey P, Gallagher N, Mathieu C, Agius MP, Zavidij O, Wang W, Jiang Y, Rajca A, Jasanoff A, Ghobrial IM, Ghoroghchian PP, Johnson JA

Polym Chem. 2020 Aug 7;11(29):4768-4779

Anti-MUC1-C Antibody-Conjugated Nanoparticles Potentiate the Efficacy of Fractionated Radiation Therapy.

Detappe A, Mathieu C, Jin C, Agius MP, Diringer MC, Tran VL, Pivot X, Lux F, Tillement O, Kufe D, Ghoroghchian PP

Int. J. Radiat. Oncol. Biol. Phys.. 2020 Jul 4;:

Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption.

Virani NA, Kelada OJ, Kunjachan S, Detappe A, Kwon J, Hayashi J, Vazquez-Pagan A, Biancur DE, Ireland T, Kumar R, Sridhar S, Makrigiorgos GM, Berbeco RI

PLoS ONE. 2020 ;15(7):e0236245

Antibody-targeting of ultra-small nanoparticles enhances imaging sensitivity and enables longitudinal tracking of multiple myeloma.

Detappe A, Reidy M, Yu Y, Mathieu C, Nguyen HV, Coroller TP, Lam F, Jarolim P, Harvey P, Protti A, Nguyen QD, Johnson JA, Cremillieux Y, Tillement O, Ghobrial IM, Ghoroghchian PP

Nanoscale. 2019 Nov 21;11(43):20485-20496

Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.

Kunjachan S, Kotb S, Pola R, Pechar M, Kumar R, Singh B, Gremse F, Taleeli R, Trichard F, Motto-Ros V, Sancey L, Detappe A, Yasmin-Karim S, Protti A, Shanmugam I, Ireland T, Etrych T, Sridhar S, Tillement O, Makrigiorgos M, Berbeco RI

Sci Rep. 2019 Nov 1;9(1):15844

Fluorescence monitoring of rare circulating tumor cell and cluster dissemination in a multiple myeloma xenograft model in vivo.

Patil R, Tan X, Bartosik P, Detappe A, Runnels JM, Ghobrial I, Lin CP, Niedre M

J Biomed Opt. 2019 08;24(8):1-11

Mitochondrial metabolism promotes adaptation to proteotoxic stress.

Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, Kocak M, Kory N, Tsherniak A, Santagata S, Whitesell L, Ghobrial IM, Markley JL, Lindquist S, Golub TR

Nat. Chem. Biol.. 2019 07;15(7):681-689

Triply Loaded Nitroxide Brush-Arm Star Polymers Enable Metal-Free Millimetric Tumor Detection by Magnetic Resonance Imaging.

Nguyen HV, Detappe A, Gallagher NM, Zhang H, Harvey P, Yan C, Mathieu C, Golder MR, Jiang Y, Ottaviani MF, Jasanoff A, Rajca A, Ghobrial I, Ghoroghchian PP, Johnson JA

ACS Nano. 2018 11 27;12(11):11343-11354

DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells.

He YJ, Meghani K, Caron MC, Yang C, Ronato DA, Bian J, Sharma A, Moore J, Niraj J, Detappe A, Doench JG, Legube G, Root DE, D'Andrea AD, Drané P, De S, Konstantinopoulos PA, Masson JY, Chowdhury D

Nature. 2018 11;563(7732):522-526

AGuIX from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.

Lux F, Tran VL, Thomas E, Dufort S, Rossetti F, Martini M, Truillet C, Doussineau T, Bort G, Denat F, Boschetti F, Angelovski G, Detappe A, Crémillieux Y, Mignet N, Doan BT, Larrat B, Meriaux S, Barbier E, Roux S, Fries P, Müller A, Abadjian MC, Anderson C, Canet-Soulas E, Bouziotis P, Barberi-Heyob M, Frochot C, Verry C, Balosso J, Evans M, Sidi-Boumedine J, Janier M, Butterworth K, McMahon S, Prise K, Aloy MT, Ardail D, Rodriguez-Lafrasse C, Porcel E, Lacombe S, Berbeco R, Allouch A, Perfettini JL, Chargari C, Deutsch E, Le Duc G, Tillement O

Br J Radiol. 2018 Sep 18;:20180365

Antibody-Dependent Cellular Phagocytosis by Macrophages is a Novel Mechanism of Action of Elotuzumab.

Kurdi AT, Glavey SV, Bezman NA, Jhatakia A, Guerriero JL, Manier S, Moschetta M, Mishima Y, Roccaro A, Detappe A, Liu CJ, Sacco A, Huynh D, Tai YT, Robbins MD, Azzi J, Ghobrial IM

Mol. Cancer Ther.. 2018 07;17(7):1454-1463

Mechanism of 53BP1 activity regulation by RNA-binding TIRR and a designer protein.

Botuyan MV, Cui G, Drané P, Oliveira C, Detappe A, Brault ME, Parnandi N, Chaubey S, Thompson JR, Bragantini B, Zhao D, Chapman JR, Chowdhury D, Mer G

Nat. Struct. Mol. Biol.. 2018 07;25(7):591-600

Advancements in Nanomedicine for Multiple Myeloma.

Detappe A, Bustoros M, Mouhieddine TH, Ghoroghchian PP

Trends Mol Med. 2018 06;24(6):560-574

Differences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer.

Tao Z, Muzumdar MD, Detappe A, Huang X, Xu ES, Yu Y, Mouhieddine TH, Song H, Jacks T, Ghoroghchian PP

Nano Lett.. 2018 04 11;18(4):2195-2208

Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas.

Meghani K, Fuchs W, Detappe A, Drané P, Gogola E, Rottenberg S, Jonkers J, Matulonis U, Swisher EM, Konstantinopoulos PA, Chowdhury D

Cell Rep. 2018 04 3;23(1):100-111

The bone-marrow niche in MDS and MGUS: implications for AML and MM.

Ghobrial IM, Detappe A, Anderson KC, Steensma DP

Nat Rev Clin Oncol. 2018 04;15(4):219-233

Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.

Qi R, Wang Y, Bruno PM, Xiao H, Yu Y, Li T, Lauffer S, Wei W, Chen Q, Kang X, Song H, Yang X, Huang X, Detappe A, Matulonis U, Pepin D, Hemann MT, Birrer MJ, Ghoroghchian PP

Nat Commun. 2017 12 18;8(1):2166

NIR-emissive PEG-b-TCL micelles for breast tumor imaging and minimally invasive pharmacokinetic analysis.

Hofmann CL, O'Sullivan MC, Detappe A, Yu Y, Yang X, Qi W, Landon CD, Therien MJ, Dewhirst MW, Ghoroghchian PP, Palmer GM

Nanoscale. 2017 Sep 21;9(36):13465-13476

The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma.

Mishima Y, Paiva B, Shi J, Park J, Manier S, Takagi S, Massoud M, Perilla-Glen A, Aljawai Y, Huynh D, Roccaro AM, Sacco A, Capelletti M, Detappe A, Alignani D, Anderson KC, Munshi NC, Prosper F, Lohr JG, Ha G, Freeman SS, Van Allen EM, Adalsteinsson VA, Michor F, San Miguel JF, Ghobrial IM

Cell Rep. 2017 04 4;19(1):218-224

Ultrasmall Silica-Based Bismuth Gadolinium Nanoparticles for Dual Magnetic Resonance-Computed Tomography Image Guided Radiation Therapy.

Detappe A, Thomas E, Tibbitt MW, Kunjachan S, Zavidij O, Parnandi N, Reznichenko E, Lux F, Tillement O, Berbeco R

Nano Lett.. 2017 03 8;17(3):1733-1740

TIRR regulates 53BP1 by masking its histone methyl-lysine binding function.

Drané P, Brault ME, Cui G, Meghani K, Chaubey S, Detappe A, Parnandi N, He Y, Zheng XF, Botuyan MV, Kalousi A, Yewdell WT, Münch C, Harper JW, Chaudhuri J, Soutoglou E, Mer G, Chowdhury D

Nature. 2017 Mar;543(7644):211-216

Established and Novel Prognostic Biomarkers in Multiple Myeloma.

Bustoros M, Mouhieddine TH, Detappe A, Ghobrial IM

Am Soc Clin Oncol Educ Book. 2017 ;37:548-560

Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery.

Appelboom G, Detappe A, LoPresti M, Kunjachan S, Mitrasinovic S, Goldman S, Chang SD, Tillement O

Neuro-oncology. 2016 12;18(12):1601-1609

Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

Detappe A, Kunjachan S, Sancey L, Motto-Ros V, Biancur D, Drane P, Guieze R, Makrigiorgos GM, Tillement O, Langer R, Berbeco R

J Control Release. 2016 09 28;238:103-113

Key clinical beam parameters for nanoparticle-mediated radiation dose amplification.

Detappe A, Kunjachan S, Drané P, Kotb S, Myronakis M, Biancur DE, Ireland T, Wagar M, Lux F, Tillement O, Berbeco R

Sci Rep. 2016 Sep 23;6:34040

Focused ultrasound to transiently disrupt the blood brain barrier.

Mitrasinovic S, Appelboom G, Detappe A, Sander Connolly E

J Clin Neurosci. 2016 06;28:187-9

Pushing radiation therapy limitations with theranostic nanoparticles.

Detappe A, Lux F, Tillement O

Nanomedicine (Lond). 2016 May;11(9):997-9

Gadolinium-Based Nanoparticles and Radiation Therapy for Multiple Brain Melanoma Metastases: Proof of Concept before Phase I Trial.

Kotb S, Detappe A, Lux F, Appaix F, Barbier EL, Tran VL, Plissonneau M, Gehan H, Lefranc F, Rodriguez-Lafrasse C, Verry C, Berbeco R, Tillement O, Sancey L

Theranostics. 2016 ;6(3):418-27

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy.

Berbeco RI, Detappe A, Tsiamas P, Parsons D, Yewondwossen M, Robar J

Med Phys. 2016 Jan;43(1):436

Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy.

Kunjachan S, Detappe A, Kumar R, Ireland T, Cameron L, Biancur DE, Motto-Ros V, Sancey L, Sridhar S, Makrigiorgos GM, Berbeco RI

Nano Lett.. 2015 Nov 11;15(11):7488-96

[Ultrasmall nanoparticles for radiotherapy: AGuIX].

Lux F, Detappe A, Dufort S, Sancey L, Louis C, Carme S, Tillement O

Cancer Radiother. 2015 Oct;19(6-7):508-14

New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect.

Altundal Y, Cifter G, Detappe A, Sajo E, Tsiamas P, Zygmanski P, Berbeco R, Cormack RA, Makrigiorgos M, Ngwa W

Phys Med. 2015 Feb;31(1):25-30

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy.

Sancey L, Lux F, Kotb S, Roux S, Dufort S, Bianchi A, Cremillieux Y, Fries P, Coll JL, Rodriguez-Lafrasse C, Janier M, Dutreix M, Barberi-Heyob M, Boschetti F, Denat F, Louis C, Porcel E, Lacombe S, Le Duc G, Deutsch E, Perfettini JL, Detappe A, Verry C, Berbeco R, Butterworth KT, McMahon SJ, Prise KM, Perriat P, Tillement O

Br J Radiol. 2014 Sep;87(1041):20140134