Syngeneic Models for Drug-Host Immune System Interactions Study December 2014 About Syngeneic Models… Rodent tumor cells • Express the mouse/rat homologues of the targets • Tumor tend to grow fast Long history of use Easy study 12/3/2014 • Strong baseline of drug response data • Wide variety of tumor types • Drug-host immune system interaction study • Relatively low cost • Reproducible page 2 Confidential SYNGENEIC MODELS AT ONCODESIGN 12/3/2014 page 3 Confidential Good characterization Characterization not complete Limited characterization Syngeneic Models at Oncodesign Model Organ Host rodent species Injection site Tested drugs 4T1 Breast carcinoma Balb/c mouse OT Radiotherapy, Doxorubicin, PD-1 mAb, CTLA-4 mAb GS-9L Gliosarcoma Ficher rat AB12 Mesothelioma Balb/c mouse SC AY27 Bladder transitional carcinoma Ficher rat OT B16-F10 Malignant melanoma C57Bl/6 mouse C26 Colon adenocarcinoma Balb/c mouse C38 Colon carcinoma C57Bl/6 mouse SC Radiotherapy, CPT-11, 5-FU, L-OHP C-51 Colon carcinoma Balb/c mouse SC CPT-11, LOHP C6 Glioma Wistar rat OT SC BCNU CT26 Colon carcinoma Balb/c mouse OT SC 5-FU, PD-1 mAb, CTLA-4 mAb Colon adenocarcinoma BDIX rat IP SC CDDP, Doxorubicin, BCG, 5-FU, L-OHP, Mitoxantrone Colon adenocarcinoma BDIX rat SC Breast carcinoma Balb/c mouse SC *DHD/K12/TRb = PROb *DHD/K12/TSb = REGb EMT6 *GV1A1 12/3/2014 Glioma BDIX rat OT SC SC IV IP OT Metastatic Dissemination BCNU, TMZ BCG, CDDP IC Paclitaxel, Doxorubicin, TMZ, Cyclophosphamide, CTLA-4 mAb SC CDDP Doxorubicin, Paclitaxel, Radiotherapy, PD-1 mAb, CTLA-4 mAb SC page 4 * Ask for rat Confidential availability Good characterization Characterization not complete Limited characterization Syngeneic Models at Oncodesign Model Organ Host rodent species Injection site Tested drugs Hepa1-6 Hepatocarcinoma C57Bl/6 mouse OT Sorafenib L1210 Lymphocytic leukemia DBA/2 mouse IP BCNU, CDDP, Doxorubicin, 5-FU L-OHP, Mitoxantrone L1210/CDDP Lymphocytic leukemia DBA/2 mouse IP CDDP, L-OHP LLC1 Lewis lung carcinoma C57Bl/6 mouse MAT-LyLu Prostate adenocarcinoma Cop rat MBT-2 Bladder carcinoma C3H mouse MPC-11 Plasmacytoma Balb/c mouse SC NBT-II Bladder carcinoma Wistar rat OT P388 Leukemia DBA/2 mouse IP BCNU, Doxorubicin, Mitoxantrone P388/ADR Leukemia DBA/2 mouse IP BCNU, Doxorubicin, Vinblastine R3327-AT3 Prostate adenocarcinoma Cop rat SC R3327H Prostate adenocarcinoma Cop rat OT SC Paclitaxel, Mitoxantrone, Trastuzumab, Leuroprolin, Castration, Decapeptyl, Bicalutamide, Radiotherapy Renca Kidney carcinoma Balb/c mouse OT SC CDDP, Paclitaxel, Radiotherapy, Gemcitabine, Carboplatin, Sorafenib IV SC Vinorelbine, Cyclophosphamide SC BCG SC OT Metastatic Dissemination Chemically Induced Tumor Models Understanding the progression of cancer and determining the most appropriate treatment periods Determination of efficacy when using chronic treatment approaches - preventive or curative Model Organ Species DMH-induced Colon Rat DMBA-induced Breast Rat Skin painting Skin Mice DEN/AAF-induced Liver Rat MNNG-induced Colon Rat AOM-induced Colon Rat Benzoα αPyrene-induced Stomach Mice Benzoα αPyrene-induced Lung Mice NNK-induced Lung Mice 12/3/2014 Tested drugs Tamoxifen, Bromocriptine, Ovariectomy, Letrozole, Faslodex page 6 Confidential
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