Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer

Porter, 2011, Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia, N. Engl. J. Med., 365, 725, 10.1056/NEJMoa1103849 Maude, 2014, Chimeric antigen receptor T cells for sustained remissions in leukemia, N. Engl. J. Med., 371, 1507, 10.1056/NEJMoa1407222 Davila, 2014, Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia, Sci. Transl. Med., 6, 224ra25, 10.1126/scitranslmed.3008226 Savoldo, 2011, CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients, J. Clin. Invest., 121, 1822, 10.1172/JCI46110 Chia, 2014, Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma, Mol. Ther., 22, 132, 10.1038/mt.2013.242 Straathof, 2005, Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes, Blood, 105, 1898, 10.1182/blood-2004-07-2975 Wente, 2005, Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer, Pancreas, 31, 119, 10.1097/01.mpa.0000173459.81193.4d Katari, 2011, Engineered T cells for pancreatic cancer treatment, HPB (Oxford), 13, 643, 10.1111/j.1477-2574.2011.00344.x Abate-Daga, 2014, A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer, Hum. Gene Ther., 25, 1003, 10.1089/hum.2013.209 Saeki, 2010, Prostate stem cell antigen: A Jekyll and Hyde molecule?, Clin. Cancer Res., 16, 3533, 10.1158/1078-0432.CCR-09-3169 Wolpin, 2013, Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer, Ann. Oncol., 24, 1792, 10.1093/annonc/mdt066 Anurathapan, 2014, Kinetics of tumor destruction by chimeric antigen receptor-modified T cells, Mol. Ther., 22, 623, 10.1038/mt.2013.262 Rucki, 2014, Pancreatic cancer stroma: Understanding biology leads to new therapeutic strategies, World J. Gastroenterol., 20, 2237, 10.3748/wjg.v20.i9.2237 Erkan, 2008, The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma, Clin. Gastroenterol. Hepatol., 6, 1155, 10.1016/j.cgh.2008.05.006 Ochi, 2012, MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells, J. Exp. Med., 209, 1671, 10.1084/jem.20111706 Gocheva, 2010, IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion, Genes Dev., 24, 241, 10.1101/gad.1874010 von Bernstorff, 2001, Systemic and local immunosuppression in pancreatic cancer patients, Clin. Cancer Res., 7, 925s Prokopchuk, 2005, Interleukin-4 enhances proliferation of human pancreatic cancer cells: Evidence for autocrine and paracrine actions, Br. J. Cancer, 92, 921, 10.1038/sj.bjc.6602416 Rabinovich, 2007, Immunosuppressive strategies that are mediated by tumor cells, Annu. Rev. Immunol., 25, 267, 10.1146/annurev.immunol.25.022106.141609 Feurino, 2006, Current update of cytokines in pancreatic cancer: Pathogenic mechanisms, clinical indication, and therapeutic values, Cancer Invest., 24, 696, 10.1080/07357900600981398 Leen, 2007, Improving T cell therapy for cancer, Annu. Rev. Immunol., 25, 243, 10.1146/annurev.immunol.25.022106.141527 Peggs, 2009, Cancer immunotherapy: Co-stimulatory agonists and co-inhibitory antagonists, Clin. Exp. Immunol., 157, 9, 10.1111/j.1365-2249.2009.03912.x Antonarakis, 2012, Phase I rapid dose-escalation study of AGS-1C4D4, a human anti-PSCA (prostate stem cell antigen) monoclonal antibody, in patients with castration-resistant prostate cancer: A PCCTC trial, Cancer Chemother. Pharmacol., 69, 763, 10.1007/s00280-011-1759-9 Yang, 2009, [Role of prostate stem cell antigen in human pancreatic carcinoma: A tissue microarray-based study], Nan Fang Yi Ke Da Xue Xue Bao, 29, 2135 Gu, 2000, Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer, Oncogene, 19, 1288, 10.1038/sj.onc.1203426 Ansari, 2015, Update on the management of pancreatic cancer: Surgery is not enough, World J. Gastroenterol., 21, 3157, 10.3748/wjg.v21.i11.3157 Siegel, 2016, Cancer statistics, 2016, CA Cancer J. Clin., 66, 7, 10.3322/caac.21332 Dotti, 2014, Design and development of therapies using chimeric antigen receptor-expressing T cells, Immunol. Rev., 257, 107, 10.1111/imr.12131 Brentjens, 2013, CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia, Sci. Transl. Med., 5, 177ra38, 10.1126/scitranslmed.3005930 Grupp, 2013, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, N. Engl. J. Med., 368, 1509, 10.1056/NEJMoa1215134 Kalos, 2011, T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia, Sci. Transl. Med., 3, 95ra73, 10.1126/scitranslmed.3002842 Kochenderfer, 2012, B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells, Blood, 119, 2709, 10.1182/blood-2011-10-384388 Chmielewski, 2012, T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice, Gastroenterology, 143, 1095, 10.1053/j.gastro.2012.06.037 Beatty, 2014, Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies, Cancer Immunol. Res., 2, 112, 10.1158/2326-6066.CIR-13-0170 Maliar, 2012, Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice, Gastroenterology, 143, 1375, 10.1053/j.gastro.2012.07.017 Nishio, 2014, Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors, Cancer Res., 74, 5195, 10.1158/0008-5472.CAN-14-0697 Song, 2011, In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB), Cancer Res., 71, 4617, 10.1158/0008-5472.CAN-11-0422 Zhao, 2009, A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity, J. Immunol., 183, 5563, 10.4049/jimmunol.0900447 Pegram, 2012, Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning, Blood, 119, 4133, 10.1182/blood-2011-12-400044 Vera, 2009, Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7, Mol. Ther., 17, 880, 10.1038/mt.2009.34 Hoyos, 2010, Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety, Leukemia, 24, 1160, 10.1038/leu.2010.75 Bollard, 2002, Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity, Blood, 99, 3179, 10.1182/blood.V99.9.3179 Lacuesta, 2006, Assessing the safety of cytotoxic T lymphocytes transduced with a dominant negative transforming growth factor-beta receptor, J. Immunother., 29, 250, 10.1097/01.cji.0000192104.24583.ca Leen, 2014, Reversal of tumor immune inhibition using a chimeric cytokine receptor, Mol. Ther., 22, 1211, 10.1038/mt.2014.47 Prosser, 2012, Tumor PD-L1 co-stimulates primary human CD8(+) cytotoxic T cells modified to express a PD1:CD28 chimeric receptor, Mol. Immunol., 51, 263, 10.1016/j.molimm.2012.03.023 Minagawa, 2015, Seatbelts in CAR therapy: How safe are cars?, Pharmaceuticals (Basel), 8, 230, 10.3390/ph8020230 Logsdon, 2003, Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer, Cancer Res., 63, 2649 van Roon, 2003, Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis, Ann. Rheum. Dis., 62, 113, 10.1136/ard.62.2.113 Lee, 2011, IL-7 promotes T(H)1 development and serum IL-7 predicts clinical response to interferon-β in multiple sclerosis, Sci. Transl. Med., 3, 93ra68, 10.1126/scitranslmed.3002400 Lin, 1995, The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15, Immunity, 2, 331, 10.1016/1074-7613(95)90141-8 Barata, 2001, Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1), Blood, 98, 1524, 10.1182/blood.V98.5.1524 Jiang, 2004, Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members, Mol. Cell. Biol., 24, 6501, 10.1128/MCB.24.14.6501-6513.2004 Wurster, 2000, The biology of Stat4 and Stat6, Oncogene, 19, 2577, 10.1038/sj.onc.1203485 Leyton, 2008, Humanized radioiodinated minibody for imaging of prostate stem cell antigen-expressing tumors, Clin. Cancer Res., 14, 7488, 10.1158/1078-0432.CCR-07-5093 Leyton, 2009, Engineered humanized diabodies for microPET imaging of prostate stem cell antigen-expressing tumors, Protein Eng. Des. Sel., 22, 209, 10.1093/protein/gzn055