Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-26T22:18:26.127Z Has data issue: false hasContentIssue false
  • English
  • Français

Opportunities and challenges in targeted therapy and immunotherapy for pancreatic cancer

Published online by Cambridge University Press:  15 December 2021

Dujuan Cao ,
Qianqian Song ,
Junqi Li ,
Yuanyuan Jiang ,
Zhimin Wang  and
Shuangshuang Lu Open the ORCID record for Shuangshuang Lu [Opens in a new window]
Dujuan Cao
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Qianqian Song
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Junqi Li
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Yuanyuan Jiang
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Zhimin Wang
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
Shuangshuang Lu*
Affiliation:
National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China
*
Author for correspondence: Shuangshuang Lu, E-mail: lushuangshuang@zzu.edu.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Pancreatic cancer is one of the most malignant tumours with a poor prognosis. In recent years, the incidence of pancreatic cancer is on the rise. Traditional chemotherapy and radiotherapy for pancreatic cancer have been improved, first-line and second-line palliative treatments have been developed, and adjuvant treatments have also been used in clinical. However, the 5-year survival rate is still less than 10% and new treatment methods such as targeted therapy and immunotherapy need to be investigated. In the past decades, many clinical trials of targeted therapies and immunotherapies for pancreatic cancer were launched and some of them showed an ideal prospect in a subgroup of pancreatic cancer patients. The experience of both success and failure of these clinical trials will be helpful to improve these therapies in the future. Therefore, the current research progress and challenges of selected targeted therapies and immunotherapies for pancreatic cancer are reviewed.

Keywords

clinical trialimmunotherapypancreatic cancertargeted therapy
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e21
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Contributed equally to this work.

References

Mizrahi, JD et al. (2020) Pancreatic cancer. Lancet (London, England) 395, 2008–2020.CrossRefGoogle ScholarPubMed
Sung, H et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians 71, 209–249.Google Scholar
Rahib, L et al. (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Research 74, 2913–2921.CrossRefGoogle ScholarPubMed
Boyle, P et al. (1989) Epidemiology of pancreas cancer (1988). International Journal of Pancreatology: Official Journal of the International Association of Pancreatology 5, 327–346.CrossRefGoogle Scholar
Kuzmickiene, I et al. (2013) Smoking and other risk factors for pancreatic cancer: a cohort study in men in Lithuania. Cancer Epidemiology 37, 133–139.CrossRefGoogle ScholarPubMed
Berrington de Gonzalez, A, Sweetland, S and Spencer, E (2003) A meta-analysis of obesity and the risk of pancreatic cancer. British Journal of Cancer 89, 519–523.CrossRefGoogle ScholarPubMed
Howe, GR et al. (1992) A collaborative case–control study of nutrient intake and pancreatic cancer within the search programme. International Journal of Cancer 51, 365–372.CrossRefGoogle ScholarPubMed
Genkinger, JM et al. (2009) Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 18, 765–776.CrossRefGoogle ScholarPubMed
Everhart, J and Wright, D (1995) Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 273, 1605–1609.CrossRefGoogle ScholarPubMed
Lowenfels, AB et al. (1993) Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. New England Journal of Medicine 328, 1433–1437.CrossRefGoogle ScholarPubMed
Goldstein, AM et al. (2006) High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Research 66, 9818–9828.CrossRefGoogle ScholarPubMed
Thompson, D, Easton, DF and Breast Cancer Linkage, C (2002) Cancer incidence in BRCA1 mutation carriers. Journal of the National Cancer Institute 94, 1358–1365.CrossRefGoogle ScholarPubMed
Breast Cancer Linkage, C (1999) Cancer risks in BRCA2 mutation carriers. Journal of the National Cancer Institute 91, 1310–1316.CrossRefGoogle Scholar
Lu, S et al. (2017) Genomic variations in pancreatic cancer and potential opportunities for development of new approaches for diagnosis and treatment. International Journal of Molecular Sciences 18, 1201.CrossRefGoogle ScholarPubMed
Tao, J et al. (2021) Targeting hypoxic tumor microenvironment in pancreatic cancer. Journal of Hematology & Oncology 14, 14.CrossRefGoogle ScholarPubMed
Baines, AT, Martin, PM and Rorie, CJ (2016) Current and emerging targeting strategies for treatment of pancreatic cancer. Progress in Molecular Biology and Translational Science 144, 277–320.CrossRefGoogle ScholarPubMed
Simpson, AJ et al. (2005) Cancer/testis antigens, gametogenesis and cancer. Nature Reviews Cancer 5, 615–625.CrossRefGoogle ScholarPubMed
Roth, MT, Cardin, DB and Berlin, JD (2020) Recent advances in the treatment of pancreatic cancer. F1000Research 9, 131.CrossRefGoogle ScholarPubMed
(2017) Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32, 185–203.e13.CrossRefGoogle Scholar
Hegde, PS and Chen, DS (2020) Top 10 challenges in cancer immunotherapy. Immunity 52, 17–35.CrossRefGoogle ScholarPubMed
Leinwand, J and Miller, G (2020) Regulation and modulation of antitumor immunity in pancreatic cancer. Nature Immunology 21, 1152–1159.CrossRefGoogle ScholarPubMed
Bear, AS, Vonderheide, RH and O'Hara, MH (2020) Challenges and opportunities for pancreatic cancer immunotherapy. Cancer Cell 38, 788–802.CrossRefGoogle ScholarPubMed
Ho, WJ, Jaffee, EM and Zheng, L (2020) The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities. Nature Reviews. Clinical Oncology 17, 527–540.CrossRefGoogle ScholarPubMed
Stella, GM et al. (2012) Targeting EGFR in non-small-cell lung cancer: lessons, experiences, strategies. Respiratory Medicine 106, 173–183.CrossRefGoogle Scholar
Pishvaian, MJ et al. (2020) Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the know your tumor registry trial. The Lancet. Oncology 21, 508–518.CrossRefGoogle ScholarPubMed
Zhu, H et al. (2020) PARP Inhibitors in pancreatic cancer: molecular mechanisms and clinical applications. Molecular Cancer 19, 49.CrossRefGoogle ScholarPubMed
Verma, HK et al. (2019) A retrospective look at anti-EGFR agents in pancreatic cancer therapy. Current Drug Metabolism 20, 958–966.CrossRefGoogle Scholar
Wang, X et al. (2018) Monensin inhibits cell proliferation and tumor growth of chemo-resistant pancreatic cancer cells by targeting the EGFR signaling pathway. Scientific Reports 8, 17914.CrossRefGoogle ScholarPubMed
Yoshida, T et al. (2020) A covalent small molecule inhibitor of glutamate-oxaloacetate transaminase 1 impairs pancreatic cancer growth. Biochemical and Biophysical Research Communications 522, 633–638.CrossRefGoogle ScholarPubMed
Patel, R et al. (2019) PARP inhibitors in pancreatic cancer: from phase I to plenary session.. Pancreas (Fairfax, Va.) 3, e5–e8.Google ScholarPubMed
Gollins, S et al. (2017) Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations. British Journal of Cancer 117, 1286–1294.CrossRefGoogle ScholarPubMed
Fung, C et al. (2012) EGFR tyrosine kinase inhibition induces autophagy in cancer cells. Cancer Biology & Therapy 13, 1417–1424.CrossRefGoogle ScholarPubMed
Takeda, Y et al. (2013) [erlotinib plus gemcitabine combination therapy in patients with unresectable advanced pancreatic cancer - a single-institution experience]. Gan to Kagaku Ryoho. Cancer & Chemotherapy 40, 1884–1886.Google Scholar
Forster, T et al. (2020) Cetuximab in pancreatic cancer therapy: a systematic review and meta-analysis. Oncology 98, 53–60.CrossRefGoogle ScholarPubMed
van Brummelen, EMJ et al. (2021) Phase I study of afatinib and selumetinib in patients with KRAS-mutated colorectal, Non-small cell lung, and pancreatic cancer. The Oncologist 26, 290– + .CrossRefGoogle ScholarPubMed
Haas, M et al. (2021) Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: the randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the ‘burden of therapy’ method. European Journal of Cancer 146, 95–106.CrossRefGoogle ScholarPubMed
Jia, Y et al. (2016) Overcoming EGFR(T790 M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature 534, 129–132.CrossRefGoogle Scholar
Wang, SH et al. (2016) Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors. Frontiers of Medicine 10, 383–388.CrossRefGoogle ScholarPubMed
Wang, SH, Song, YP and Liu, DL (2017) EAI045: the fourth-generation EGFR inhibitor overcoming T790 M and C797S resistance. Cancer Letters 385, 51–54.CrossRefGoogle Scholar
Gibbs-Seymour, I et al. (2016) HPF1/C4orf27 Is a PARP-1-interacting protein that regulates PARP-1 ADP-ribosylation activity. Molecular cell 62, 432–442.CrossRefGoogle ScholarPubMed
McCann, K and Hurvitz, S (2018) Advances in the use of PARP inhibitor therapy for breast cancer. Drugs in context 7, 212540.CrossRefGoogle ScholarPubMed
Min, A et al. (2018) Androgen receptor inhibitor enhances the antitumor effect of PARP inhibitor in breast cancer cells by modulating DNA damage response. Molecular cancer therapeutics 17, 2507–2518.CrossRefGoogle ScholarPubMed
Golan, T et al. (2019) Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. New England Journal of Medicine 381, 317–327.CrossRefGoogle ScholarPubMed
Le, D and Gelmon, K (2018) Olaparib tablets for the treatment of germ line BRCA-mutated metastatic breast cancer. Expert review of clinical pharmacology 11, 833–839.CrossRefGoogle ScholarPubMed
Golan, T et al. (2021) Overall survival from the phase 3 POLO trial: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. Journal of Clinical Oncology 39, suppl. 378.CrossRefGoogle Scholar
Zinatizadeh, MR et al. (2019) The role and function of Ras-association domain family in cancer: a review. Genes & Diseases 6, 378–384.CrossRefGoogle ScholarPubMed
Janssen, KP et al. (2005) Mouse models of K-ras-initiated carcinogenesis. Biochimica et Biophysica Acta 1756, 145–154.Google ScholarPubMed
Li, T et al. (2016) K-Ras mutation detection in liquid biopsy and tumor tissue as prognostic biomarker in patients with pancreatic cancer: a systematic review with meta-analysis. Medical Oncology (Northwood, London, England) 33, 61.CrossRefGoogle ScholarPubMed
Herbst, RS and Schlessinger, J (2019) Small molecule combats cancer-causing KRAS protein at last. Nature 575, 294–295.CrossRefGoogle ScholarPubMed
Canon, J et al. (2019) The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575, 217–223.CrossRefGoogle ScholarPubMed
Hong, DS et al. (2020) KRAS(G12C) inhibition with sotorasib in advanced solid tumors. New England Journal of Medicine 383, 1207–1217.CrossRefGoogle ScholarPubMed
Blair, HA (2021) Sotorasib: first approval. Drugs 81, 1573–1579.CrossRefGoogle ScholarPubMed
Hallin, J et al. (2020) The KRAS(G12C) inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discovery 10, 54–71.CrossRefGoogle ScholarPubMed
Singh, RR and O'Reilly, EM (2020) New treatment strategies for metastatic pancreatic ductal adenocarcinoma. Drugs 80, 647–669.CrossRefGoogle ScholarPubMed
Kawaguchi, K et al. (2018) MEK Inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model. Tissue & Cell 52, 124–128.CrossRefGoogle ScholarPubMed
Chao, MW et al. (2019) Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status. Clinical Epigenetics 11, 85.CrossRefGoogle ScholarPubMed
Bryant, KL et al. (2019) Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nature Medicine 25, 628– + .CrossRefGoogle ScholarPubMed
Foster, SA et al. (2016) Activation mechanism of oncogenic deletion mutations in BRAF, EGFR, and HER2. Cancer Cell 29, 477–493.CrossRefGoogle ScholarPubMed
Harder, J et al. (2012) Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer. British Journal of Cancer 106, 1033–1038.CrossRefGoogle ScholarPubMed
Assenat, E et al. (2021) Phase II study evaluating the association of gemcitabine, trastuzumab and erlotinib as first-line treatment in patients with metastatic pancreatic adenocarcinoma (GATE 1). International Journal of Cancer 148, 682–691.CrossRefGoogle Scholar
Itatani, Y et al. (2018) Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF pathway. International journal of molecular sciences 19, 1232.CrossRefGoogle ScholarPubMed
Lian, L et al. (2019) VEGFR2 Promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer. BMC Cancer 19, 183.CrossRefGoogle Scholar
Pan, YL et al. (2015) A preclinical evaluation of SKLB261, a multikinase inhibitor of EGFR/Src/VEGFR2, as a therapeutic agent against pancreatic cancer. Molecular Cancer Therapeutics 14, 407–418.CrossRefGoogle ScholarPubMed
Gao, F and Yang, C (2020) Anti-VEGF/VEGFR2 monoclonal antibodies and their combinations with PD-1/PD-L1 inhibitors in clinic. Current Cancer Drug Targets 20, 3–18.CrossRefGoogle ScholarPubMed
Crane, CH et al. (2006) Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. Journal of Clinical Oncology 24, 1145–1151.CrossRefGoogle ScholarPubMed
Crane, CH et al. (2009) Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: radiation therapy oncology group RTOG 0411. Journal of Clinical Oncology 27, 4096–4102.CrossRefGoogle ScholarPubMed
Kindler, HL et al. (2005) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. Journal of Clinical Oncology 23, 8033–8040.CrossRefGoogle ScholarPubMed
Ko, AH et al. (2008) A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable? Investigational New Drugs 26, 463–471.CrossRefGoogle ScholarPubMed
Fogelman, D et al. (2011) Bevacizumab plus gemcitabine and oxaliplatin as first-line therapy for metastatic or locally advanced pancreatic cancer: a phase II trial. Cancer Chemotherapy and Pharmacology 68, 1431–1438.CrossRefGoogle ScholarPubMed
Tortora, G, Ciardiello, F and Gasparini, G (2008) Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications. Nature Clinical Practice. Oncology 5, 521–530.CrossRefGoogle ScholarPubMed
Watkins, DJ et al. (2014) The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study. European Journal of Cancer 50, 1422–1429.CrossRefGoogle ScholarPubMed
Starling, N et al. (2009) Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Journal of Clinical Oncology 27, 5499–5505.CrossRefGoogle ScholarPubMed
Ko, AH et al. (2012) A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. Investigational New Drugs 30, 1597–1606.CrossRefGoogle ScholarPubMed
Seto, E and Yoshida, M (2014) Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harbor Perspectives in Biology 6, a018713.CrossRefGoogle ScholarPubMed
Delcuve, GP, Khan, DH and Davie, JR (2012) Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clinical Epigenetics 4, 5.CrossRefGoogle ScholarPubMed
Mottamal, M et al. (2015) Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 20, 3898–3941.CrossRefGoogle ScholarPubMed
Moertl, S et al. (2019) Comparison of radiosensitization by HDAC inhibitors CUDC-101 and SAHA in pancreatic cancer cells. International Journal of Molecular Sciences 20, 3259.CrossRefGoogle ScholarPubMed
Marks, PA and Breslow, R (2007) Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nature Biotechnology 25, 84–90.CrossRefGoogle ScholarPubMed
Edderkaoui, M et al. (2018) An inhibitor of GSK3B and HDACs kills pancreatic cancer cells and slows pancreatic tumor growth and metastasis in mice. Gastroenterology 155, 1985–1998, e5.CrossRefGoogle ScholarPubMed
Ikeda, M et al. (2019) Phase I study of resminostat, an HDAC inhibitor, combined with S-1 in patients with pre-treated biliary tract or pancreatic cancer. Investigational New Drugs 37, 109–117.CrossRefGoogle ScholarPubMed
Booth, L, Poklepovic, A and Dent, P (2020) Neratinib decreases pro-survival responses of [sorafenib + vorinostat] in pancreatic cancer. Biochemical Pharmacology 178, 114067.CrossRefGoogle Scholar
Chan, E et al. (2016) Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Radiotherapy & Oncology 119, 312–318.CrossRefGoogle ScholarPubMed
Chen, Z et al. (2021) A neoantigen-based peptide vaccine for patients with advanced pancreatic cancer refractory to standard treatment. Frontiers in Immunology 12, 691605.CrossRefGoogle ScholarPubMed
(2020) Pan-cancer analysis of whole genomes. Nature 578, 82–93.CrossRefGoogle Scholar
Moskaluk, CA, Hruban, RH and Kern, SE (1997) P16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Research 57, 2140–2143.Google ScholarPubMed
Suehara, N et al. (1998) Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer. American Journal of Gastroenterology 93, 1967–1971.CrossRefGoogle Scholar
Rong, Y et al. (2012) A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer. Clinical and Experimental Medicine 12, 173–180.CrossRefGoogle ScholarPubMed
Weden, S et al. (2011) Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. International Journal of Cancer 128, 1120–1128.CrossRefGoogle ScholarPubMed
Gjertsen, MK et al. (2001) Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: clinical and immunological responses in patients with pancreatic adenocarcinoma. International Journal of Cancer 92, 441–450.CrossRefGoogle ScholarPubMed
Abou-Alfa, GK et al. (2011) Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine. American Journal of Clinical Oncology 34, 321–325.CrossRefGoogle ScholarPubMed
Gjertsen, MK et al. (1995) Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Lancet (London, England) 346, 1399–1400.CrossRefGoogle ScholarPubMed
Gjertsen, MK et al. (1997) Cytotoxic CD4 + and CD8 + T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. International Journal of Cancer 72, 784–790.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Gjertsen, MK et al. (1996) Ex vivo ras peptide vaccination in patients with advanced pancreatic cancer: results of a phase I/II study. International Journal of Cancer 65, 450–453.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Bernhardt, SL et al. (2006) Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose-escalating phase I/II study. British Journal of Cancer 95, 1474–1482.CrossRefGoogle ScholarPubMed
Lepisto, AJ et al. (2008) A phase I/II study of a MUC1 peptide-pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors. Cancer Therapy 6, 955–964.Google ScholarPubMed
Yamamoto, K et al. (2005) MUC1 Peptide vaccination in patients with advanced pancreas or biliary tract cancer. Anticancer Research 25, 3575–3579.Google ScholarPubMed
Srivatsan, S et al. (2014) Allogeneic tumor cell vaccines: the promise and limitations in clinical trials. Human Vaccines & Immunotherapeutics 10, 52–63.CrossRefGoogle ScholarPubMed
Laheru, D et al. (2008) Allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clinical Cancer Research 14, 1455–1463.CrossRefGoogle ScholarPubMed
Lutz, ER et al. (2014) Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunology Research 2, 616–631.CrossRefGoogle ScholarPubMed
Lutz, E et al. (2011) A lethally irradiated allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A phase II trial of safety, efficacy, and immune activation. Annals of Surgery 253, 328–335.Google ScholarPubMed
Le, DT et al. (2013) Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. Journal of Immunotherapy 36, 382–389.CrossRefGoogle ScholarPubMed
Le, DT et al. (2015) Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 33, 1325–1333.CrossRefGoogle ScholarPubMed
Le, DT et al. (2019) Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE Study). Clinical Cancer Research 25, 5493–5502.CrossRefGoogle Scholar
Tsujikawa, T et al. (2020) Evaluation of cyclophosphamide/GVAX pancreas followed by Listeria-mesothelin (CRS-207) with or without nivolumab in patients with pancreatic cancer. Clinical Cancer Research 26, 3578–3588.CrossRefGoogle ScholarPubMed
Lu, S et al. (2020) A virus-infected, reprogrammed somatic cell-derived tumor cell (VIReST) vaccination regime can prevent initiation and progression of pancreatic cancer. Clinical Cancer Research 26, 465–476.CrossRefGoogle ScholarPubMed
Nakamura, M et al. (2009) Long-term outcome of immunotherapy for patients with refractory pancreatic cancer. Anticancer Research 29, 831–836.Google ScholarPubMed
Kimura, Y et al. (2012) Clinical and immunologic evaluation of dendritic cell-based immunotherapy in combination with gemcitabine and/or S-1 in patients with advanced pancreatic carcinoma. Pancreas 41, 195–205.CrossRefGoogle ScholarPubMed
Kondo, H et al. (2008) Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. Anticancer Research 28, 379–387.Google ScholarPubMed
Allum, WH et al. (1986) Demonstration of carcinoembryonic antigen (CEA) expression in normal, chronically inflamed, and malignant pancreatic tissue by immunohistochemistry. Journal of Clinical Pathology 39, 610–614.CrossRefGoogle ScholarPubMed
Qu, CF et al. (2004) MUC1 Expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate. British Journal of Cancer 91, 2086–2093.CrossRefGoogle ScholarPubMed
Chmielewski, M et al. (2012) T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice. Gastroenterology 143, 1095–1107, e2.CrossRefGoogle ScholarPubMed
Posey, AD Jr. et al. (2016) Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity 44, 1444–1454.CrossRefGoogle Scholar
Disis, ML (2014) Mechanism of action of immunotherapy. Seminars in Oncology 41(Suppl 5), S3–13.CrossRefGoogle ScholarPubMed
Weber, J (2008) Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with ipilimumab (MDX-010). The Oncologist 13(Suppl 4), 16–25.CrossRefGoogle Scholar
Royal, RE et al. (2010) Phase 2 trial of single-agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. Journal of Immunotherapy 33, 828–833.CrossRefGoogle ScholarPubMed
Aglietta, M et al. (2014) A phase I dose-escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer. Annals of Oncology: Official Journal of the European Society for Medical Oncology 25, 1750–1755.CrossRefGoogle ScholarPubMed
Clark, CE, Beatty, GL and Vonderheide, RH (2009) Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Letters 279, 1–7.CrossRefGoogle ScholarPubMed
Kawaoka, T et al. (2008) Adoptive immunotherapy for pancreatic cancer: cytotoxic T lymphocytes stimulated by the MUC1-expressing human pancreatic cancer cell line YPK-1. Oncology Reports 20, 155–163.Google ScholarPubMed
Brahmer, JR et al. (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New England Journal of Medicine 366, 2455–2465.CrossRefGoogle ScholarPubMed