Skip to main content

Advertisement

SpringerLink
Log in

Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. Immunosuppressive tumor microenvironment and dense fibrous stroma are some of the limitation in the success of this novel therapy. However, genetic modifications and combination therapy is the topic of the research to improve its efficacy. In this article, we summarize the current state of knowledge, limitations, and future prospects for CAR T cell therapy in pancreatic cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386.

    Article  PubMed  CAS  Google Scholar 

  2. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. Seer cancer statistics review, 1975–2012. Bethesda: National Cancer Institute; 2015.

    Google Scholar 

  3. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144(6):1252–61.

    Article  PubMed  Google Scholar 

  4. Bazhin AV, Shevchenko I, Umansky V, Werner J, Karakhanova S. Two immune faces of pancreatic adenocarcinoma: possible implication for immunotherapy. Cancer Immunol Immunother. 2014;63:59–65. https://doi.org/10.1007/s00262-013-1485-8.

    Article  PubMed  CAS  Google Scholar 

  5. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371:1039–49. https://doi.org/10.1056/NEJMra1404198.

    Article  PubMed  CAS  Google Scholar 

  6. Vaccaro V, Sperduti I, Milella M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;365(8):768–9.

    Article  PubMed  CAS  Google Scholar 

  7. Chang JH, Jiang Y, Pillarisetty VG. Role of immune cells in pancreatic cancer from bench to clinical application: an updated review. Medicine. 2016;95:e5541.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Campoli M, Ferrone S. HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene. 2008;27:5869–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Chang CC, Campoli M, Ferrone S. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions. Adv Cancer Res. 2005;93:189–234.

    Article  PubMed  CAS  Google Scholar 

  10. Zhao Z, Condomines M, van der Stegen SJ, Perna F, Kloss CC, Gunset G, et al. Structural design of engineered costimulation determines tumor rejec-tion kinetics and persistence of CAR T cells. Cancer Cell 2015;28(4):415–28. https://doi.org/10.1016/j.ccell.2015.09.0042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–98. https://doi.org/10.1158/2159-8290.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Chmielewski M, Hombach AA, Abken H. Antigen-specific T-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. Front Immunol. 2013;4:371. https://doi.org/10.3389/fimmu.2013.00371.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Riddell SR, Sommermeyer D, Berger C, Liu LS, Balakrishnan A, Salter A, Hudecek M, Maloney DG, Turtle CJ. Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition. Cancer J. 2014;20:141–4. https://doi.org/10.1097/PPO.0000000000000036.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Kershaw MH, Westwood JA, Slaney CY, Darcy PK. Clinical application of genetically modified T cells in cancer therapy. Clin Transl Immunol. 2014;3(5):e16.

    Article  CAS  Google Scholar 

  15. Yasukawa M, Ohminami H, Arai J, Kasahara Y, Ishida Y, Fujita S. Granule exocytosis, and not the fas/fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4(+) as well as CD8(+)cytotoxic T lymphocytes in humans. Blood. 2000;95(7):2352–5.

    PubMed  CAS  Google Scholar 

  16. Hombach A, Kohler H, Rappl G, Abken H. Human CD4 + T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. J Immunol. 2006;177(8):5668–75.

    Article  PubMed  CAS  Google Scholar 

  17. Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood. 2014;123(17):2625–35. https://doi.org/10.1182/blood-2013-11-492231 5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Pegram HJ, Park JH, Brentjens RJ. CD28z CARs and armored CARs. Cancer J. 2014;20(2):127. https://doi.org/10.1097/PPO.0000000000000034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Nummer D, Suri-Payer E, Schmitz-Winnenthal H, et al. Role of tumor endothelium in CD4 + CD25 + regulatory T cell infiltration of human pancreatic carcinoma. J Natl Cancer Inst. 2007;99:1188–99.

    Article  PubMed  CAS  Google Scholar 

  20. Panni RZ, Sanford DE, Belt BA, et al. Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother. 2014;63:513–28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Ryschich E, Notzel T, Hinz U, et al. Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma. Clin Cancer Res. 2005;11:498–504.

    PubMed  CAS  Google Scholar 

  22. von Bernstorff W, Spanjaard RA, Chan AK, et al. Pancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand. Surgery. 1999;125:73–84.

    Article  Google Scholar 

  23. Bellone G, Turletti A, Artusio E, et al. Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am J Pathol. 1999;155:537–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Moo-Young TA, Larson JW, Belt BA, et al. Tumor-derived TGF-beta mediates conversion of CD4 + Foxp3 + regulatory T cells in a murine model of pancreas cancer. J Immunother. 2009;32:12–21.

    Article  PubMed  CAS  Google Scholar 

  25. Uyttenhove C, Pilotte L, Theate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269–74.

    Article  PubMed  CAS  Google Scholar 

  26. Witkiewicz A, Williams TK, Cozzitorto J, et al. Expression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J Am Coll Surg. 2008;206:849–54.

    Article  PubMed  Google Scholar 

  27. Basso D, Fogar P, Falconi M, et al. Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen: role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study. PLoS One. 2013;8:e54824.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin Cancer Res. 2012;18:4266–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Clark CE, Hingorani SR, Mick R, et al. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67:9518–27.

    Article  PubMed  CAS  Google Scholar 

  30. Chang K, Pastan I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA. 1996;93:136–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Cheng WF, Huang CY, Chang MC, et al. High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma. Br J Cancer. 2009;100:1144–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Winter JM, Tang LH, Klimstra DS, et al. A novel survival-based tissue microarray of pancreatic cancer validates MUC1 and mesothelin as biomarkers. PLoS One. 2012;7:e40157. [Erratum: PLoS One 7, 2012].

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Shimizu A, Hirono S, Tani M, et al. Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma. Cancer Sci. 2012;103:739–46.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Kawamata F, Kamachi H, Einama T, et al. Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer. Int J Oncol. 2012;41:2109–18.

    Article  PubMed  Google Scholar 

  35. Nomura R, Fujii H, Abe M, et al. Mesothelin expression is a prognostic factor in cholangiocellular carcinoma. Int Surg. 2013;98:164–9.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Thomas A, Chen Y, Steinberg SM, et al. High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis. Oncotarget. 2015;6:11694–703.

    PubMed  PubMed Central  Google Scholar 

  37. Kachala SS, Bograd AJ, Villena-Vargas J, et al. Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma. Clin Cancer Res. 2014;20:1020–8. (Erratum 20:3896, 2014).

    Article  PubMed  CAS  Google Scholar 

  38. Li YR, Xian RR, Ziober A, et al. Mesothelin expression is associated with poor outcomes in breast cancer. Breast Cancer Res Treat. 2014;147:675–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Kolivas E, Rudloff M, Poruchynsky M, et al. Mesothelin-targeted immunotoxin RG7797 has synergistic anti-tumor activity when combined with taxanes. Oncotarget. 2017;8(6):9189–99.

    Google Scholar 

  40. 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;33:1325–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Hassan R, Ebel W, Routhier EL, et al. Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin. Cancer Immunol. 2007;19:7–20.

    Google Scholar 

  42. Francisco JA, Cerveny CG, Meyer DL, et al. cAC10-vcMMAE, an anti CD30 monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102:1458–65.

    Article  PubMed  CAS  Google Scholar 

  43. Zhao XY, Subramanyam B, Sarapa N, Golfier S, Dinter H. Novel antibody therapeutics targeting mesothelin in solid tumors. Clin Cancer Drugs. 2016;3(2):76–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2:112–20.

    Article  PubMed  CAS  Google Scholar 

  45. Kim CF, Jackson EL, Woolfenden AE, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121(6):823–35. https://doi.org/10.1016/j.cell.2005.03.032.

    Article  PubMed  CAS  Google Scholar 

  46. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–10. https://doi.org/10.1038/nature05372.

    Article  PubMed  CAS  Google Scholar 

  47. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Can Res. 2005;65(23):10946–51. https://doi.org/10.1158/0008-5472.CAN-05-2018.

    Article  CAS  Google Scholar 

  48. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 2006;103(30):11154–9. https://doi.org/10.1073/pnas.0603672103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Can Res. 2007;67(3):1030–7. https://doi.org/10.1158/0008-5472.CAN-06-2030.

    Article  CAS  Google Scholar 

  50. Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1(3):313–23. https://doi.org/10.1016/j.stem.2007.06.002.

    Article  PubMed  CAS  Google Scholar 

  51. Maliar A, Servais C, Waks T, et al. Redirected T cells that target pancreatic adenocarcinoma antigens eliminate tumors and metastases in mice. Gastroenterology. 2012;143:1375.e1371–1384.e1375.

    Article  CAS  Google Scholar 

  52. Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9:67–81. https://doi.org/10.1006/scbi.1998.0119.

    Article  PubMed  CAS  Google Scholar 

  53. Albers GH, Fleuren G, Escribano MJ, Nap M. Immunohistochemistry of CEA in the human pancreas during development, in the adult, chronic pancreatitis, and pancreatic adenocarcinoma. Am J Clin Pathol. 1988;90:17–22.

    Article  PubMed  CAS  Google Scholar 

  54. Allum WH, Stokes HJ, Macdonald F, Fielding JW. Demonstration of carcinoembryonic antigen (CEA) expression in normal, chronically inflamed, and malignant pancreatic tissue by immunohistochemistry. J Clin Pathol. 1986;39:610–4. https://doi.org/10.1136/jcp.39.6.610.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Yamaguchi K, Enjoji M, Tsuneyoshi M. Pancreatoduodenal carcinoma: a clinicopathologic study of 304 patients and immunohistochemical observation for CEA and CA19-9. J Surg Oncol. 1991;47:148–54. https://doi.org/10.1002/jso.2930470303.

    Article  PubMed  CAS  Google Scholar 

  56. Chmielewski M, Hahn O, Rappl G, et al. T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice. Gastroenterology. 2012;143:1095.e2–1107.e2.

    Article  CAS  Google Scholar 

  57. Thistlethwaite F. A CRUK phase I trial of adoptive transfer of autologous tumour antigen-specific T cells with pre-conditioning chemotherapy and intravenous IL2 in patients with advanced CEA positive tumours. In: NCRI Poster Session; 2010.

  58. Hawkins R. A trial looking at MFEz T cells, chemotherapy and IL-2 (interleukin 2) for cancers that test positive for carcinoembryonic antigen (CEA) (PH1/105). In: Cancer Research UK Clinical Trial Listings; 2010.

  59. Gendler SJ. MUC1, the renaissance molecule. J Mammary Gland Biol Neoplasia. 2001;6:339–53.

    Article  PubMed  CAS  Google Scholar 

  60. Qu CF, Li Y, Song YJ, Rizvi SM, Raja C, Zhang D, et al. MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by (213)Bi-C595 radioimmunoconjugate. Br J Cancer. 2004;91:2086–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Pichinuk E, Benhar I, Jacobi O, Chalik M, Weiss L, Ziv R, et al. Antibody targeting of cell-bound MUC1 SEA domain kills tumor cells. Cancer Res. 2012;72:3324–36. https://doi.org/10.1158/0008-5472.CAN-12-0067.

    Article  PubMed  CAS  Google Scholar 

  62. Posey AD Jr, Schwab RD, Boesteanu AC, et al. Engineered CAR T cells targeting the cancer-associated Tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016;44:1444–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Bittoni A, Mandolesi A, Andrikou K, Santoni M, Alfonsi S, Lanese A, et al. HER family receptor expression and prognosis in pancreatic cancer. Int J Biol Markers. 2015;30:e327–32.

    Article  CAS  Google Scholar 

  64. Rajagopal I, Niveditha SR, Sahadev R, Nagappa PK, Rajendra SG. HER 2 expression in gastric and gastro-esophageal junction (gej) adeno- carcinomas. J Clin Diagn Res. 2015;9:EC06–10.

    PubMed  PubMed Central  Google Scholar 

  65. Te Velde EA, Franke AC, van Hillegersberg R, et al. HER-family gene amplification and expression in resected pancreatic cancer. Eur J Surg Oncol. 2009;35:1098–104.

    Article  PubMed  CAS  Google Scholar 

  66. Safran H, Steinhoff M, Mangray S, et al. Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma. Am J Clin Oncol. 2001;24:496–9.

    Article  PubMed  CAS  Google Scholar 

  67. Komoto M, Nakata B, Amano R, et al. HER2 overexpression correlates with survival after curative resection of pancreatic cancer. Cancer Sci. 2009;100:1243–7.

    Article  PubMed  CAS  Google Scholar 

  68. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014:124: 188–95.

  69. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.

    Article  PubMed  CAS  Google Scholar 

  71. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Curran KJ, Pegram HJ, Brentjens RJ. Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med. 2012;14:405–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010. 2010;18:843–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 1997;276:1719–24.

    Article  PubMed  CAS  Google Scholar 

  75. Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M, Bordignon C, et al. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood. 2001;97:1249–57.

    Article  PubMed  CAS  Google Scholar 

  76. Serafini M, Manganini M, Borleri G, Bonamino M, Imberti L, Biondi A, et al. Characterization of CD20-transduced T lymphocytes as an alternative suicide gene therapy approach for the treatment of graft-versus-host disease. Hum Gene Ther 2004. 2004;15:63–76.

    Article  PubMed  CAS  Google Scholar 

  77. John LB, Devaud C, Duong CP, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by genemodified T cells. Clin Cancer Res. 2013;19:5636–46.

    Article  PubMed  CAS  Google Scholar 

  78. Vatner RE, Cooper BT, Vanpouille-Box C, et al. Combinations of immunotherapy and radiation in cancer therapy. Front Oncol. 2014;4:325.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7.

    Article  PubMed  CAS  Google Scholar 

  80. Sandin LC, Eriksson F, Ellmark P, et al. Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo. Oncoimmunology. 2014;3:e27614.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Bunt SK, Mohr AM, Bailey JM, et al. Rosiglitazone and gemcitabine in combination reduces immune suppression and modulates T cell populations in pancreatic cancer. Cancer Immunol Immunother. 2013;62:225–36.

    Article  PubMed  CAS  Google Scholar 

  82. Eikawa S, Nishida M, Mizukami S, et al. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci USA. 2015;112:1809–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Craddock JA, Lu A, Bear A, Pule M, Brenner MK, Rooney CM, et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. Journal of immunotherapy (Hagerstown:1997). 2010; 33: 780.

    Article  CAS  Google Scholar 

  84. Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113:6392 – 402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Moon EK, Carpenito C, Sun J, Wang L-CS, Kapoor V, Predina J, et al. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin- specific chimeric antibody receptor. Clin Cancer Res. 2011;17(14):4719–30. https://doi.org/10.1158/1078-0432.CCR-11-0351.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Yurchenco PD, Schittny JC. Molecular architecture of basement membranes. FASEB J. 1990;4:1577–90.

    Article  PubMed  CAS  Google Scholar 

  87. Caruana I, Savoldo B, Hoyos V, Weber G, Liu H, Kim ES, et al. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lym-phocytes. Nat Med. 2015;21(5):524–9. https://doi.org/10.1038/nm.3833.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

Special thanks to Dr. Manisha Dhananjaya.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Saint Vincent Hospital, 123 Summer Street, Worcester, 01608, USA

    Vishal Jindal

  2. Department of Internal Medicine, Government Medical College, Chandigarh, India

    Ena Arora

  3. Department of Internal Medicine, Einstein Healthcare Network, Philadelphia, USA

    Muhammad Masab

  4. Department of Hematology and Oncology, Einstein Healthcare Network, Philadelphia, USA

    Sorab Gupta

Authors
  1. Vishal Jindal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ena Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad Masab
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sorab Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vishal Jindal.

Ethics declarations

Conflict of interest

There is no conflict of interest among authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jindal, V., Arora, E., Masab, M. et al. Chimeric antigen receptor T cell therapy in pancreatic cancer: from research to practice. Med Oncol 35, 84 (2018). https://doi.org/10.1007/s12032-018-1145-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-018-1145-0

Keywords

Search

Navigation