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Pierre Martineau

Name of the laboratory

Institut de Recherche en Cancérologie de Montpellier
Immunotargeting and Radiobiology in Oncology
Institut de Recherche en Cancérologie de Montpellier, IRCM
INSERM U896/Montpellier University/Val d’Aurelle Oncology Center
208 rue des Apothicaires
34298 Montpellier Cedex 5, France
33.(0)4.67.61.85.77

Members of the laboratory

Head
André PELEGRIN andre.pelegrin@inserm.fr
Unit Leader
Christel LARBOURET christel.larbouret@inserm.fr
Christian LARROQUE christian.larroque@inserm.fr
Engineers
Madeline NEIVEYANS madeline.neiveyans@inserm.fr
Technicians
PhD students
Cécile GALMICHE cecile.galmiche@inserm.fr

Laboratory activity

Oncologists prescribe mAbs to their patients as routinely as chemotherapy. Antibodies represented almost half of the top-20 US therapeutic biotechnology sales for 2007. This state-of-the-art situation is radically different from that of the 1990’s when only few people and companies were convinced of the therapeutic potential of mAbs. However, there is still place for improvements in mAb-based cancer therapies since about half of cancer patients are not cured yet. Indeed, mAbs present the unique opportunity of a potential triple mechanism of action: (i) a direct effect on the target antigen and its intracellular signaling pathways; (ii) an effect on the immune system (i.e., antibody-dependent cellular cytotoxicity –ADCC- and complement-dependent cytolysis -CDC); and (iii) they can be armed with toxins or radioisotopes to enhance their action.

In this context, our strategy includes (i) the development and evaluation of proprietary molecules for which we can set up partnerships with biotech companies and envisage the long term transfer to the clinic and (ii) the original use and evaluation of approved molecules which can be translated into the clinic more rapidly.

Research activities

In our institute, we developed phage display approach, to select antibodies. Our bank is fully human, and allows us to make an effective screening on in vivo tumor models. SPEC-CT technology provides us a good technology to follow tumor growth and antibody targeting in the small animal. Using an in vitro selection system allows us to systematically select for antibodies that cross react with human and mouse proteins. This greatly facilitates the in vivo characterization of the monoclonal antibodies in pertinent pre-clinical models.

Techniques available

  • Monoclonal antibody production in mice
  • Antibodies characterization
  • Phage display
  • Immunization with transfected cells
  • Antibody purification
  • Testing candidate therapeutic antibodies in pre-clinical xenograft models
  • www.ircm.fr

Publications (2014-present)

  • Lacombe J, Riou O, Solassol J, Mangé A, Bourgier C, Fenoglietto P, Pèlegrin A, Ozsahin M, Azria D. Intrinsic radiosensitivity: Predictive assays that will change the daily practice. Cancer Radiother. 2013 Aug 30. pii:S1278-3218(13)00311-9. doi: 10.1016/j.canrad.2013.07.137. [Epub ahead of print]
  • Boudousq V, Bobyk L, Busson M, Garambois V, Jarlier M, Charalambatou P, Pèlegrin A, Paillas S, Chouin N, Quenet F, Maquaire P, Torgue J, Navarro-Teulon I, Pouget JP. Comparison between Internalizing Anti-HER2 mAbs and Non-Internalizing Anti-CEA mAbs in Alpha-Radioimmunotherapy of Small Volume Peritoneal Carcinomatosis Using (2) (1) (2)Pb. PLoS One. 2013 Jul 29;8(7):e69613. doi: 10.1371/journal.pone.0069613. Print 2013.
  • Navarro-Teulon I, Lozza C, Pèlegrin A, Vivès E, Pouget JP. General overview of radioimmunotherapy of solid tumors. Immunotherapy. 2013 May;5(5):467-87. doi: 10 22 17 /imt .13. 34.
  • Paillas S, Boudousq V, Piron B, Kersual N, Bardiès M, Chouin N, Bascoul-Mollevi C, Arnaud FX, Pèlegrin A, Navarro-Teulon I, Pouget JP. Apoptosis and p53 are not involved in the anti-tumor efficacy of 125I-labeled monoclonal antibodies targeting the cell membrane. Nucl Med Biol. 2013 Mar 19. doi:pii: S0969-8051(13)00017-6. 10.1016/j.nucmedbio. 2013 .02.001. [Epub ahead of print]
  • Lazrek Y, Dubreuil O, Garambois V, Gaborit N, Larbouret C, Le Clorennec C, Thomas G, Leconet W, Jarlier M, Pugnière M, Vié N, Robert B, Monnet C, Bouayadi K, Kharrat H, Mondon P, Pèlegrin A, Chardès T. Anti-HER3 Domain 1 and 3 Antibodies Reduce Tumor Growth by Hindering HER2/HER3 Dimerization and AKT-Induced MDM2, XIAP, and FoxO1 Phosphorylation. Neoplasia. 2013 Mar;15(3):335-47.
  • Del Rio M, Mollevi C, Vezzio-Vie N, Bibeau F, Ychou M, Martineau P. Specific extracellular matrix remodeling signature of colon hepatic metastases. PLoS One. 2013 Sep 4;8(9):e74599. doi: 10. 1371/journal.pone.0074599.
  • Mazard T, Causse A, Simony J, Leconet W, Vezzio-Vie N, Torro A, Jarlier M, Evrard A, Del Rio M, Assenat E, Martineau P, Ychou M, Robert B, Gongora C Sorafenib overcomes irinotecan resistance in colorectal cancer by inhibiting the ABCG2 drug-efflux pump. Mol Cancer Ther. 2013 Aug 19. [Epub ahead of print]
  • Lynne Cassimeris, Laurence Guglielmi, Vincent Denis, Christian Larroque, Pierre Martineau. Specific In Vivo Labeling of Tyrosinated α-Tubulin and Measurement of Microtubule Dynamics Using a GFP Tagged, Cytoplasmically Expressed Recombinant Antibody. Plos One March 28, 2013
  • Larbouret C, Gaborit N, Chardès T, Coelho M, Campigna E, Bascoul-Mollevi C, Mach JP, Azria D, Robert B, Pèlegrin A. In Pancreatic Carcinoma, Dual EGFR/HER2 Targeting with Cetuximab/Trastuzumab Is More Effective than Treatment with Trastuzumab/Erlotinib or Lapatinib Alone: Implication of Receptors' Down-regulation and Dimers' Disruption. Neoplasia. 2012 Feb;14(2):121-30.
  • Robin G, Martineau P. Synthetic customized scFv libraries. Methods Mol Biol. 2012;907:109-22. doi: 10.1007/978-1-61779-974-76.
  • Kamel Deramchia , Marie-Josee Jacobin-Valat, Jeanny Laroche-Traineau, Stephane Bonetto, Stephane Sanchez1 , Pierre Dos Santos , Philippe Massot, Jean-Michel Franconi, Pierre Martineau, Gisele Clofent-Sanchez. By-Passing Large Screening Experiments Using Sequencing as a Tool to Identify scFv Fragments Targeting Atherosclerotic Lesions in a Novel In Vivo Phage Display Selection. Int. J. Mol. Sci. 2012, 13(6), 6902-6923;
  • Paillas S, Causse A, Marzi L, de Medina P, Poirot M, Denis V, Vezzio-Vie N, Espert L, Arzouk H, Coquelle A, Martineau P, Del Rio M, Pattingre S, Gongora C. MAPK14/p38α confers irinotecan resistance to TP53-defective cells by inducing survival autophagy. Autophagy. 2012 Jul 1;8(7). [Epub ahead of print]
  • Pouget JP, Navarro-Teulon I, Bardiès M, Chouin N, Cartron G, Pèlegrin A, Azria D. Clinical radioimmunotherapy-the role of radiobiology. Nat Rev Clin Oncol. 2011 Nov 8. 8;8(12):720-34.
  • Rigo M, Chentouf M, Pèlegrin A, Chardès T. CD4 ligation excludes the Carma1-Bcl10-MALT1 complex from GM1-positive membrane rafts in CD3/CD28 activated T cells. Cell Immunol. 2011;270(1):40-6.
  • Ladjemi MZ, Chardes T, Corgnac S, Garambois V, Morisseau S, Robert B, Bascoul-Mollevi C, Ait Arsa I, Jacot W, Pouget JP, Pelegrin A, Navarro-Teulon I. Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice. Breast Cancer Res. 2011 Feb 4;13(1):R17.
  • Gaborit N, Larbouret C, Vallaghe J, Peyrusson F, Bascoul-Mollevi C, Crapez E, Azria D, Chardes T, Poul MA, Mathis G, Bazin H, Pèlegrin A. Time resolved fluorescence resonance energy transfer (TR-FRET) to analyze the disruption of EGFR/HER2 dimers: a new method to evaluate the efficiency of targeted therapy using monoclonal antibodies. J Biol Chem. 2011 Jan 31. Apr 1;286 (13): 11337-45.
  • Guglielmi L, Denis V, Vezzio-Vié N, Bec N, Dariavach P, Larroque C, Martineau P. Selection for intrabody solubility in mammalian cells using GFP fusions. Protein Eng Des Sel. 2011 Dec;24(12):873-81.
  • Villoutreix BO, Laconde G, Lagorce D, Martineau P, Miteva MA, Dariavach P. Tyrosine kinase syk non-enzymatic inhibitors and potential anti-allergic drug-like compounds discovered by virtual and in vitro screening. PLoS One. 2011;6(6):e21117. Epub 2011 Jun 20.
  • Gongora C, Vezzio-Vie N, Tuduri S, Denis V, Causse A, Auzanneau C, Collod-Beroud G, Coquelle A, Pasero P, Pourquier P, Martineau P, Del Rio M. New Topoisomerase I mutations are associated with resistance to camptothecin. Gongora C, Mol Cancer. 2011 May 27;10(1):64. [Epub ahead of print]
  • Estephan E, Saab MB, Martin M, Larroque C, Cuisinier FJ, Briot O, Ruffenach S, Moret M, Gergely C. 2010. Phages recognizing the Indium Nitride semiconductor surface via their peptides. J Pept Sci 30: 30
  • Rogowski K, van Dijk J, Magiera MM, Bosc C, Deloulme JC, Bosson A, Peris L, Gold ND, Lacroix B, Grau MB, Bec N, Larroque C, Desagher S, Holzer M, Andrieux A, Moutin MJ, Janke C.. A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell. 2010;143: 564-578.
  • Paillas S, Boissiere F, Bibeau F, Denouel A, Mollevi C, Causse A, Denis V, Vezzio-Vie N, Marzi L, Cortijo C, Ait-Arsa I, Askari N, Pourquier P, Martineau P, Del Rio M, Gongora C. 2010. Targeting the p38 MAPK pathway inhibits irinotecan resistance in colon adenocarcinoma. Cancer Res 2011 Feb 1;71(3):1041-9.
  • Boudousq V, Ricaud S, Garambois V, Bascoul-Mollevi C, Boutaleb S, Busson M, Quenet F, Colombo PE, Bardiès M, Kotzki PO, Navarro-Teulon I, Pèlegrin A, Pouget JP. Brief Intraperitoneal Radioimmunotherapy of Small Peritoneal Carcinomatosis Using High Activities of Noninternalizing 125I-Labeled Monoclonal Antibodies. J Nucl Med. 2010 Nov; 51(11):1748-55
  • Chentouf M, Rigo M, Ghannam S, Navarro-Teulon I, Mongrand S, Pèlegrin A, Chardès T. The lipid-modulating effects of a CD4-specific recombinant antibody correlate with ZAP-70 segregation outside membrane rafts. Immunol Lett. 2010 Oct 30;133(2):62-9.
  • Larbouret C, Robert B, Bascoul-Mollevi C, Penault-Llorca F, Ho-Pun-Cheung A, Morisseau S, Navarro-Teulon I, Mach JP, Pèlegrin A, Azria D. Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts. Ann Oncol. 2010 Jan;21(1):98-103
  • Thierry AR, Mouliere F, Gongora C, Ollier J, Robert B, Ychou M, Del Rio M, Molina F. Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts. Nucleic Acids Res. 2010 Oct;38(18):6159-75
  • Bonfils C, Bec N, Larroque C, Rio MD, Gongora C, Pugnière M, Martineau P. Cyclophilin A as negative regulator of apoptosis by sequestering cytochrome c. Biochem Biophys Res Commun. 2010 Mar 5;393(2):325-30.
  • Amina Bouslimani, Nicole Bec, Matthias Glueckmann, Christophe Hirtz and Christian Larroque. Matrix-assisted laser desorption/ionization imaging mass spectrometry of oxaliplatin derivatives in heated intraoperative chemotherapy (HIPEC)-like treated rat kidney. Rapid Commun. Mass Spectrom. 2010; 24: 415­421
  • Santoro L, Boutaleb S, Garambois V, Bascoul-Mollevi C, Boudousq V, Kotzki PO, Pèlegrin M, Navarro-Teulon I, Pèlegrin A, Pouget JP. Noninternalizing Monoclonal Antibodies Are Suitable Candidates for 125I Radioimmunotherapy of Small-Volume Peritoneal Carcinomatosis. J Nucl Med. 2009 Dec;50(12):2033-41
  • Stork R, Campigna E, Robert B, Mueller D, Kontermann RE. Biodistribution of a bispecific single-chain diabody and its half-life extended derivatives. J Biol Chem. 2009. Sep 18;284(38):25612-9
  • Alvarez-Rueda N, Ladjemi MZ, Behar G, Corgnac S, Pugniere M, Roquet F, Bascoul-Mollevi C, Baty D, Pelegrin A, Navarro-Teulon I. A llama single domain anti-idiotypic antibody mimicking HER2 as a vaccine: Immunogenicity and efficacy. Vaccine 2009. Jul 30;27(35):4826-33
  • Larbouret C, Robert B, Bascoul-Mollevi C, Penault-Llorca F, Ho-Pun-Cheung A, Morisseau S, Navarro-Teulon I, Mach JP, Pèlegrin A, Azria D. Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts. Ann Oncol. 2009 Nov 4. [Epub ahead of print]
  • Biodistribution of a bispecific single-chain diabody and its half-life extended derivatives.Stork R, Campigna E, Robert B, Mueller D, Kontermann RE.J Biol Chem. 2009 Jul 23
  • Alvarez-Rueda N, Ladjemi MZ, Behar G, Corgnac S, Pugniere M, Roquet F, Bascoul-Mollevi C, Baty D, Pelegrin A, Navarro-Teulon I. A llama single domain anti-idiotypic antibody mimicking HER2 as a vaccine: Immunogenicity and efficacy. Vaccine 2009. In Press
  • Faruque OM, Le-Nguyen D, Lajoix AD, Vives E, Petit P, Bataille D, Hani el H. Cell-permeable peptide-based disruption of endogenous PKA-AKAP complexes: a tool for studying the molecular roles of AKAP-mediated PKA subcellular anchoring. Am J Physiol Cell Physiol 2009; 296: C306-316.
  • Estephan E, Saab MB, Larroque C, Martin M, Olsson F, Lourdudoss S, Gergely C. Peptides for functionalization of InP semiconductors. J Colloid Interface Sci. 2009 Sep 15;337(2):358-63
  • Estephan E, Larroque C, Bec N, Martineau P, Cuisinier FJ, Cloitre T, Gergely C. Selection and mass spectrometry characterization of peptides targeting semiconductor surfaces. Biotechnol Bioeng. 2009 Dec 15;104(6):1121-31
  • Estephan E, Larroque C, Cuisinier FJ, Bálint Z, Gergely C. Tailoring GaN semiconductor surfaces with biomolecules. J Phys Chem B. 2008 Jul 24;112(29):8799-805
  • Granci V, Bibeau F, Krama A, Boissiere-Michot F,Thezenas S, Thirion A, Gongora C, Martineau P, Del RioM, Ychou M. Prognostic significance of TRAIL-R1 andTRAIL-R3 expression in metastatic colorectal carcinomas. Eur J Cancer 2008; 44: 2312-2318
  • Mazuc E, Villoutreix BO, Malbec O, Roumier T, Fleury S, Leonetti JP, Dombrowicz D, Daeron M, Martineau P, Dariavach P. A novel druglike spleen tyrosine kinase binder prevents anaphylactic shock when administered orally.J Allergy Clin Immunol 2008 In PRESS
  • Gongora, C., Candeil, L., Vezzio, N., Copois, V., Denis, V., Bareil, C., Molina, F., Fraslon, C., Conseiller, E., Pau, B., Martineau, P., and Del Rio, M. Altered expression of cell proliferation-related and interferon-stimulated genes in colon cancer cells resistant to SN38. Cancer Biol Ther, 7, 2008.
  • Vie, N., Copois, V., Mollevi, C., Denis, V., Bec, N., Robert, B., Fraslon, C., Conseiller, E., Molina, F., Larroque, C., Martineau, P., Del Rio, M., and Gongora, C. Overexpression of phosphoserine aminotransferase PSAT1 stimulates cell growth and increases chemoresistance of colon cancer cells. Mol Cancer, 7: 14, 2008.
  • Azria D, Ozsahin M, Kramar A, Peters S, Atencio DP, Crompton NE, Mornex F, Pelegrin A, Dubois JB, Mirimanoff RO, Rosenstein BS. Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy. Clin Cancer Res 2008; 14: 6284-6288.
  • Pouget JP, Santoro L, Raymond L, Chouin N, Bardies M, Bascoul-Mollevi C, Huguet H, Azria D, Kotzki PO, Pelegrin M, Vives E, Pelegrin A. Cell Membrane is a More Sensitive Target than Cytoplasm to Dense Ionization Produced by Auger Electrons. Radiat Res 2008; 170: 192-200.
  • Ychou M, Azria D, Menkarios C, Faurous P, Quenet F, Saint-Aubert B, Rouanet P, Pelegrin M, Bascoul-Mollevi C, Guerreau D, Saccavini JC, Mach JP, Artus JC, Pelegrin A. Adjuvant Radioimmunotherapy Trial with Iodine-131-Labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody F6 F(ab')2 after Resection of Liver Metastases from Colorectal Cancer. Clin Cancer Res 2008; 14: 3487-3493.
  • Kucharczak J, Charrasse S, Comunale F, Zappulla J, Robert B, Teulon-Navarro I, Pelegrin A, Gauthier-Rouviere C. R-Cadherin expression inhibits myogenesis and induces myoblast transformation via Rac1 GTPase. Cancer Res 2008; 68: 6559-6568.