An overview of up-and-coming immune checkpoint inhibitors for pancreatic cancer

References

• Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018 Mar 23;359(6382):1350–1355.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Chen M, Nie H, et al. PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations. Hum Vaccin Immunother. 2019;15(5):1111–1122. doi: 10.1080/21645515.2019.1571892
   PubMed Web of Science ®Google Scholar
• Huo JL, Wang YT, Fu WJ, et al. The promising immune checkpoint LAG-3 in cancer immunotherapy: from basic research to clinical application. Front Immunol. 2022;13:956090. doi: 10.3389/fimmu.2022.956090
   PubMed Web of Science ®Google Scholar
• Liu JK. Anti-cancer vaccines - a one-hit wonder? Yale J Biol Med. 2014 Dec;87(4):481–489.
   PubMedGoogle Scholar
• Dudley ME, Rosenberg SA. Adoptive cell transfer therapy. Semin Oncol. 2007 Dec;34(6):524–31. doi: 10.1053/j.seminoncol.2007.09.002
   PubMed Web of Science ®Google Scholar
• Petrelli F, Ghidini M, Ghidini A, et al. Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and meta-analysis. JAMA Oncol. 2020 Jul 1;6(7):1068–1071. doi: 10.1001/jamaoncol.2020.1046
   PubMed Web of Science ®Google Scholar
• Royal RE, Levy C, Turner K, et al. Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010 Oct;33(8):828–33.
   PubMed Web of Science ®Google Scholar
• Keam SJ. Tremelimumab: First Approval. Drugs. 2023 Jan;83(1):93–102. doi: 10.1007/s40265-022-01827-8
   PubMed Web of Science ®Google Scholar
• Li H, van der Merwe PA, Sivakumar S. Biomarkers of response to PD-1 pathway blockade. Br J Cancer. 2022 Jun;126(12):1663–1675. doi: 10.1038/s41416-022-01743-4
   PubMed Web of Science ®Google Scholar
• Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847–856. doi: 10.1158/1535-7163.MCT-14-0983
   PubMed Web of Science ®Google Scholar
• Mucileanu A, Chira R, Mircea PA. PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies. Med Pharm Rep. 2021 Oct;94(4):402–410. doi: 10.15386/mpr-2116
   PubMedGoogle Scholar
• Tessier-Cloutier B, Kalloger SE, Al-Kandari M, et al. Programmed cell death ligand 1 cut-point is associated with reduced disease specific survival in resected pancreatic ductal adenocarcinoma. BMC Cancer. 2017 Sep 5;17(1):618. doi: 10.1186/s12885-017-3634-5
   PubMedGoogle Scholar
• Zhang Y, Chen X, Mo S, et al. PD-L1 and PD-L2 expression in pancreatic ductal adenocarcinoma and their correlation with immune infiltrates and DNA damage response molecules. J Pathol Clin Res. 2022 May;8(3):257–267.
   PubMedGoogle Scholar
• Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti–PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–2465. doi: 10.1056/NEJMoa1200694
   PubMed Web of Science ®Google Scholar
• O’Reilly EM, Oh DY, Dhani N, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2019 Oct 1;5(10):1431–1438. doi: 10.1001/jamaoncol.2019.1588
   PubMed Web of Science ®Google Scholar
• Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008 Aug;224(1):166–82. doi: 10.1111/j.1600-065X.2008.00662.x
   PubMedGoogle Scholar
• Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy–inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012 Dec 15;18(24):6580–6587.
   PubMed Web of Science ®Google Scholar
• Das R, Verma R, Sznol M, et al. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015 Feb 1;194(3):950–959. doi: 10.4049/jimmunol.1401686
   PubMed Web of Science ®Google Scholar
• Nabrinsky E, Macklis J, Bitran J. A review of the abscopal effect in the Era of Immunotherapy. Cureus. 2022 Sep;14(9):e29620. doi: 10.7759/cureus.29620
   PubMed Web of Science ®Google Scholar
• Du J, Lu C, Mao L, et al. PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: a biomolecular exploratory, phase II trial. Cell Rep Med. 2023 Mar 21;4(3):100972. doi: 10.1016/j.xcrm.2023.100972
   PubMedGoogle Scholar
• Duffy AG, Makarova-Rusher OV, Kleiner DE, et al. A pilot study of immune checkpoint inhibition in combination with radiation therapy in patients with metastatic pancreatic cancer. J Clin Oncol. 2017;35(15_suppl):e15786–e15786. doi: 10.1200/JCO.2017.35.15_suppl.e15786
   Google Scholar
• Chen IM, Johansen JS, Theile S, et al. Randomized phase II study of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy for refractory metastatic pancreatic cancer (CheckPAC). J Clin Oncol. 2022;40(27):3180–3189. doi: 10.1200/JCO.21.02511
   PubMed Web of Science ®Google Scholar
• Chen IM, Donia M, Chamberlain CA, et al. Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R). Eur J Cancer. 2023 Feb;180:125–133.
   PubMed Web of Science ®Google Scholar
• Ansari D, Carvajo M, Bauden M, et al. Pancreatic cancer stroma: controversies and current insights. Scand J Gastroenterol. 2017;52(6–7):641–646. doi: 10.1080/00365521.2017.1293726
   PubMed Web of Science ®Google Scholar
• Waghray M, Yalamanchili M, di Magliano MP, et al. Deciphering the role of stroma in pancreatic cancer. Curr Opin Gastroenterol. 2013 Sep;29(5):537–543.
   PubMed Web of Science ®Google Scholar
• Ene–Obong A, Clear AJ, Watt J, et al. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology. 2013;145(5):1121–1132. doi: 10.1053/j.gastro.2013.07.025
   PubMed Web of Science ®Google Scholar
• Skelton RA, Javed A, Zheng L, et al. Overcoming the resistance of pancreatic cancer to immune checkpoint inhibitors. J Surg Oncol. 2017;116(1):55–62. doi: 10.1002/jso.24642
   PubMed Web of Science ®Google Scholar
• Edwards P, Kang BW, Chau I. Targeting the stroma in the Management of pancreatic cancer. Front Oncol. 2021;11:691185. doi: 10.3389/fonc.2021.691185
   PubMed Web of Science ®Google Scholar
• Rahma OE, Katz MHG, Wolpin BM, et al. Randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer. J Clin Oncol. 2021;39(15_suppl):4128–4128. doi: 10.1200/JCO.2021.39.15_suppl.4128
   Web of Science ®Google Scholar
• Aglietta M, Barone C, Sawyer MB, et al. A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer. Ann Oncol. 2014 Sep;25(9):1750–1755.
   PubMed Web of Science ®Google Scholar
• Kamath SD, Kalyan A, Kircher S, et al. Ipilimumab and gemcitabine for advanced pancreatic cancer: a phase ib study. Oncology. 2020 May;25(5):e808–e815.
   Google Scholar
• Weiss GJ, Blaydorn L, Beck J, et al. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018 Feb;36(1):96–102.
   PubMed Web of Science ®Google Scholar
• Renouf DJ, Dhani NC, Kavan P, et al. The Canadian cancer trials group PA.7 trial: results from the safety run in of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (nab-P) versus GEM, nab-P, durvalumab (D), and tremelimumab (T) as first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC). J Clin Oncol. 2018;36(4_suppl):349–349.
   Web of Science ®Google Scholar
• Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013 Mar 1;19(5):1035–43.
   PubMed Web of Science ®Google Scholar
• O’Hara MH, O’Reilly EM, Varadhachary G, et al. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021 Jan;22(1):118–131.
   PubMed Web of Science ®Google Scholar
• Padrón LJ, Maurer DM, O’Hara MH, et al. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167–1177.
   PubMed Web of Science ®Google Scholar
• Wang-Gillam A, Plambeck-Suess S, Goedegebuure P, et al. A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. Invest New Drugs. 2013 Jun;31(3):707–13.
   PubMed Web of Science ®Google Scholar
• de la Chapelle A. Microsatellite instability. N Engl J Med. 2003;349(3):209–210. doi: 10.1056/NEJMp038099
   PubMed Web of Science ®Google Scholar
• Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409–413. doi: 10.1126/science.aan6733
   PubMed Web of Science ®Google Scholar
• FDA U. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. Silver Spring: US Food and Drug Administration; 2017.
   Google Scholar
• Prasad V, Kaestner V. Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Semin Oncol. 2017 Apr;44(2):132–135. doi: 10.1053/j.seminoncol.2017.06.007. Epub 2017 Jul 13. PMID: 28923211 .
   Web of Science ®Google Scholar
• Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9(1):1–14. doi: 10.1186/s13073-017-0424-2
   PubMed Web of Science ®Google Scholar
• Chang L, Chang M, Chang HM, et al. Microsatellite instability: a predictive biomarker for cancer immunotherapy. Appl Immunohistochem Mol Morphol. 2018;26(2):e15–e21. doi: 10.1097/PAI.0000000000000575
   PubMedGoogle Scholar
• Hu ZI, Shia J, Stadler ZK, et al. Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations. Clin Cancer Res. 2018 Mar 15;24(6):1326–1336. doi: 10.1158/1078-0432.CCR-17-3099
   PubMed Web of Science ®Google Scholar
• Cavalieri CC. Pembrolizumab in gastrointestinal (GI) malignancies with defective DNA mismatch repair (dMMR): a single institution experience. J Clin Oncol. 2017;35(15_suppl):e23081–e23081. doi: 10.1200/JCO.2017.35.15_suppl.e23081
   Google Scholar
• Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 2022 Sep;33(9):929–938.
   PubMed Web of Science ®Google Scholar
• Quintanilha JCF, Storandt MH, Graf RP, et al. Tumor mutational burden in real-world patients with pancreatic cancer: genomic alterations and predictive value for immune checkpoint inhibitor effectiveness. JCO Precision Oncol. 2023;7(7):e2300092. doi: 10.1200/PO.23.00092
   PubMedGoogle Scholar
• Coston T, Desai A, Babiker H, et al. Efficacy of immune checkpoint inhibition and cytotoxic chemotherapy in mismatch repair-deficient and microsatellite instability-high pancreatic cancer: mayo clinic experience. JCO Precision Oncol. 2023;7(7):e2200706. doi: 10.1200/PO.22.00706
   PubMedGoogle Scholar
• Oaknin A, Gilbert L, Tinker AV, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022 Jan;10(1). doi: 10.1136/jitc-2021-003777
   PubMed Web of Science ®Google Scholar
• Zhu H, Wei M, Xu J, et al. PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications. Mol Cancer. 2020 Mar 2;19(1):49. doi: 10.1186/s12943-020-01167-9
   PubMed Web of Science ®Google Scholar
• Wu Z, Cui P, Tao H, et al. The synergistic effect of PARP inhibitors and immune checkpoint inhibitors. Clin Med Insights Oncol. 2021;15:1179554921996288. doi: 10.1177/1179554921996288
   Web of Science ®Google Scholar
• Sokol ES, Pavlick D, Khiabanian H, et al. Pan-cancer Analysis of BRCA1 and BRCA2 genomic alterations and their association with genomic instability as measured by genome-wide loss of Heterozygosity. JCO Precis Oncol. 2020;4(4):442–465. doi: 10.1200/PO.19.00345
   PubMedGoogle Scholar
• Terrero G, Datta J, Dennison J, et al. Ipilimumab/Nivolumab therapy in patients with metastatic pancreatic or biliary cancer with homologous recombination deficiency pathogenic germline variants. JAMA Oncol. 2022 Jun 1;8(6):1–3. doi: 10.1001/jamaoncol.2022.0611
   PubMed Web of Science ®Google Scholar
• Reiss KA, Mick R, Teitelbaum U, et al. Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial. Lancet Oncol. 2022 Aug;23(8):1009–1020. doi: 10.1016/S1470-2045(22)00369-2
   PubMed Web of Science ®Google Scholar
• Mahalingam D, Fountzilas C, Moseley JL, et al. Astudy of REOLYSIN in combination with pembrolizumab and chemotherapy in patients (pts) with relapsed metastatic adenocarcinoma of the pancreas (MAP). Jou of Clini Onco. 2017. May 35(15_suppl):e15753–e15753.
   Google Scholar
• Liu L, Huang X, Shi F, et al. Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy. J Exp Clin Cancer Res. 2022 Feb 9;41(1):56. doi: 10.1186/s13046-022-02273-w
   PubMed Web of Science ®Google Scholar
• Woo Y, Zhang Z, Yang A, et al. Novel Chimeric Immuno-Oncolytic Virus CF33-hNIS-antiPDL1 for the treatment of pancreatic cancer. J Am Coll Surg. 2020 Apr;230(4):709–717.
   PubMed Web of Science ®Google Scholar
• Calmeiro J, Carrascal MA, Tavares AR, et al. Pharmacological combination of nivolumab with dendritic cell vaccines in cancer immunotherapy: an overview. Pharmacol Res. 2021 Feb;164:105309.
   PubMed Web of Science ®Google Scholar
• Nemunaitis J. Vaccines in cancer: GVAX, a GM-CSF gene vaccine. Expert Rev Vaccines. 2005 Jun;4(3):259–274. doi: 10.1586/14760584.4.3.259
   PubMed Web of Science ®Google Scholar
• Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX pancreas prime and listeria monocytogenes–expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015;33(12):1325–1333. doi: 10.1200/JCO.2014.57.4244
   PubMed Web of Science ®Google Scholar
• Le DT, Lutz E, Uram JN, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013 Sep;36(7):382–9.
   PubMed Web of Science ®Google Scholar
• Tsujikawa T, Crocenzi T, Durham JN, et al. Evaluation of Cyclophosphamide/GVAX pancreas followed by listeria-mesothelin (CRS-207) with or without nivolumab in patients with pancreatic cancer. Clin Cancer Res. 2020 Jul 15;26(14):3578–3588. doi: 10.1158/1078-0432.CCR-19-3978
   PubMed Web of Science ®Google Scholar
• Ma HS, Torres ER, Poudel B, et al. Abstract 4936: combination CD40 agonist and PD-1 antagonist antibody therapy enhances vaccine induced T cell responses in non-immunogenic cancers. Cancer Res. 2018;78(13_Supplement):4936–4936. doi: 10.1158/1538-7445.AM2018-4936
   Web of Science ®Google Scholar
• Borazanci EH, Jameson G, Korn RL, et al. Abstract CT152: A Phase II pilot trial of nivolumab (N)+ albumin bound paclitaxel (AP)+ paricalcitol (P)+ cisplatin (C)+ gemcitabine (G)(NAPPCG) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC). Cancer Res. 2019;79(13_Supplement):CT152–CT152. doi: 10.1158/1538-7445.AM2019-CT152
   Web of Science ®Google Scholar
• Hong DS, Rixe O, Chiu VK, et al. Mogamulizumab in combination with nivolumab in a phase I/II study of patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2022 Feb 1;28(3):479–488. doi: 10.1158/1078-0432.CCR-21-2781
   PubMed Web of Science ®Google Scholar
• Overman MJ, LoRusso P, Strickler JH, et al. Safety, efficacy and pharmacodynamics (PD) of MEDI9447 (oleclumab) alone or in combination with durvalumab in advanced colorectal cancer (CRC) or pancreatic cancer (panc). J Clin Oncol. 2018;36(15_suppl):4123–4123. doi: 10.1200/JCO.2018.36.15_suppl.4123
   Web of Science ®Google Scholar
• Hornyák L, Dobos N, Koncz G, et al. The role of indoleamine-2,3-dioxygenase in cancer development, Diagnostics, and therapy. Front Immunol. 2018;9:151. doi: 10.3389/fimmu.2018.00151
   PubMed Web of Science ®Google Scholar
• Naing A, Powderly JD, Falchook G, et al. Abstract CT177: epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study. Cancer Res. 2018;78(13_Supplement):CT177–CT177. doi: 10.1158/1538-7445.AM2018-CT177
   Web of Science ®Google Scholar
• Razak AR, Cleary JM, Moreno V, et al. Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001006.
   PubMed Web of Science ®Google Scholar
• Strauss J, Heery CR, Schlom J, et al. Phase I trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in advanced solid tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287–1295. doi: 10.1158/1078-0432.CCR-17-2653
   PubMed Web of Science ®Google Scholar
• Ko AH, Kim KP, Siveke JT, et al. Atezolizumab Plus PEGPH20 versus Chemotherapy in advanced pancreatic ductal adenocarcinoma and gastric cancer: MORPHEUS phase Ib/II umbrella randomized study platform. Oncology. 2023 Jun 2;28(6):553–e472. doi: 10.1093/oncolo/oyad022
   Google Scholar
• Halama N, Williams A, Suarez-Carmona M, et al. 1537P phase I/II study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer. Ann Oncol. 2020;31:S944. doi: 10.1016/j.annonc.2020.08.2020
   Google Scholar
• Bockorny B, Semenisty V, Macarulla T, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020 Jun;26(6):878–885.
   PubMed Web of Science ®Google Scholar
• Overman M, Javle M, Davis RE, et al. Randomized phase II study of the Bruton tyrosine kinase inhibitor acalabrutinib, alone or with pembrolizumab in patients with advanced pancreatic cancer. J Immunother Cancer. 2020 Feb;8(1):e000587.
   PubMed Web of Science ®Google Scholar
• Zachary I. Focal adhesion kinase. Int J Biochem Cell Biol. 1997 Jul;29(7):929–34. doi: 10.1016/S1357-2725(97)00008-3
   PubMed Web of Science ®Google Scholar
• Wang-Gillam A, Lim KH, McWilliams R, et al. Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study. Clin Cancer Res. 2022 Dec 15;28(24):5254–5262. doi: 10.1158/1078-0432.CCR-22-0308
   PubMed Web of Science ®Google Scholar
• Canon J, Rex K, Saiki AY, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217–223.
   PubMed Web of Science ®Google Scholar
• Yuwen H, Li T, Ren Y, et al. 893 ATG-101, a novel PD-L1/4–1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4–1BB activation. J Immunother Cancer. 2021;9(Suppl 2):A936–A937. doi: 10.1136/jitc-2021-SITC2021.893
   Google Scholar
• Yuwen H, Li T, Ren Y, et al. 1397 ATG 027 a first in class B7 H3 PD L1 bispecific antibody shows potent T cell activation capability and in vivo anti tumor efficacy. J Immunother Cancer. 2022;10(Suppl 2):A1452–A1452.
   Google Scholar
• Thakur A, Ung J, Tomaszewski EN, et al. Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness. Oncoimmunology. 2021 Jun 1;10(1):1930883. doi: 10.1080/2162402X.2021.1930883
   PubMed Web of Science ®Google Scholar
• Pang N, Shi J, Qin L, et al. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol. 2021 Jul 29;14(1):118. doi: 10.1186/s13045-021-01128-9
   PubMed Web of Science ®Google Scholar
• Haas AR, Tanyi JL, O’Hara MH, et al. Phase I study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in advanced solid cancers. Mol Ther. 2019 Nov 6;27(11):1919–1929. doi: 10.1016/j.ymthe.2019.07.015
   PubMed Web of Science ®Google Scholar
• Feng K, Liu Y, Guo Y, et al. Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers. Protein Cell. 2018 Oct;9(10):838–847.
   PubMed Web of Science ®Google Scholar
• Katz SC, Moody AE, Guha P, et al. HITM-SURE: hepatic immunotherapy for metastases phase ib anti-CEA CAR-T study utilizing pressure enabled drug delivery. J Immunother Cancer. 2020 Aug;8(2):e001097.
   PubMed Web of Science ®Google Scholar
• Parriott G, Deal K, Crean S, et al. T-cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumour burden in multiple murine syngeneic models of solid cancer. Immunology. 2020 Jul;160(3):280–294.
   PubMed Web of Science ®Google Scholar
• Yang CY, Fan MH, Miao CH, et al. Engineering Chimeric Antigen Receptor T Cells against immune checkpoint inhibitors PD-1/PD-L1 for treating pancreatic cancer. Mol Ther Oncolytics. 2020 Jun 26;17:571–585.
   PubMed Web of Science ®Google Scholar
• Yoo B, Jordan VC, Sheedy P, et al. RNAi-mediated PD-L1 inhibition for pancreatic cancer immunotherapy. Sci Rep. 2019 Mar 18;9(1):4712. doi: 10.1038/s41598-019-41251-9
   PubMedGoogle Scholar
• Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023 Jun;618(7963):144–150.
   PubMed Web of Science ®Google Scholar
• Babiker HM, Zahid U, Howe CL, et al. Analyzing the efficacy and safety of immunotherapy in pancreatic ductal adenocarcinoma (PDA): a systematic review and meta-analysis. J Clin Oncol. 2018;36(4_suppl):512–512. doi: 10.1200/JCO.2018.36.4_suppl.512
   PubMed Web of Science ®Google Scholar
• Li C, Cui L, Yang L, et al. Pancreatic stellate cells promote tumor progression by promoting an immunosuppressive microenvironment in murine models of pancreatic cancer. Pancreas. 2020 Jan;49(1):120–127.
   PubMed Web of Science ®Google Scholar
• Milone MC, Xu J, Chen SJ, et al. Engineering enhanced CAR T-cells for improved cancer therapy. Nat Cancer. 2021 Aug;2(8):780–793.
   PubMedGoogle Scholar