Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Intraperitoneal immunotherapy: historical perspectives and modern therapy

Abstract

Intraperitoneal immunotherapy represents a novel strategy for the management of peritoneal metastases (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has remained the gold standard of treatment for patients with PM, yet despite optimal treatment, recurrence rates remain high and long-term survival poor. From Coley’s toxins to immune checkpoint inhibitors, the wide variety of anticancer immunotherapeutic strategies are now garnering attention for control of regional disease of the peritoneal cavity. Early studies with vaccine-based therapies, adoptive cell transfer, immune checkpoint inhibitors, and chimeric T cells with tumor-specific antigen receptors (CAR-T cells) are being performed, showing promise for control of peritoneal spread and induction of lasting anticancer immunity. In addition, catumaxomab, a trifunctional antibody, has been approved for intraperitoneal immunotherapy in Europe for the control of malignant ascites in patients with epithelial cell adhesion molecule positive cancers. We review a brief history of immunotherapy and current modalities under investigation for intraperitoneal use in the treatment of PM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Krieg AM . CpG motifs: the active ingredient in bacterial extracts? Nat Med 2003; 9: 831–835.

    CAS  PubMed  Google Scholar 

  2. Hoption Cann SA, van Netten JP, van Netten C . Dr William Coley and tumor regression: a place in history or in the future? Postgrad Med J 2003; 79: 672–680.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Linehan DC, Bowne WB, Lewis JJ . Immunotherapeutic approaches to sarcoma. Semin Surg Oncol 1999; 17: 72–77.

    CAS  PubMed  Google Scholar 

  4. Kucerova P, Cervinkova M . Spontaneous regression of tumor and the role of microbial infection - possibilities for cancer treatment. Anticancer Drugs 2016; 27: 269–277.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hall SS . The man who does the most work does the best work. In: A Commotion in the Blood: Life, Death, and the Immune System. Henry Holt and Company, Inc: New York, NY, USA, 1997.

    Google Scholar 

  6. Coley WB . The treatment of malignant tumors by repeated inoculations of erysipelas, with a report of ten original cases. Am J Med Sci 1893; 105: 487–511.

    Google Scholar 

  7. Old LJ, Clarke DA, Benacerraf B . Effect of Bacillus Calmette-Guerin infection on transplanted tumours in the mouse. Nature 1959; 164: 291–292.

    Google Scholar 

  8. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B . An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975; 72: 3666–3670.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Vijayasaradhi S, Bouchard B, Houghton AN . The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. J Exp Med 1990; 171: 1375–1380.

    CAS  PubMed  Google Scholar 

  10. Naftzger C, Takechi Y, Kohda H, Hara I, Vijayasaradhi S, Houghton AN . Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. Proc Natl Acad Sci USA 1996; 93: 14809–14814.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Weber LW, Bowne WB, Wolchok JD, Srinivasan R, Qin J, Moroi Y et al. Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest 1998; 102: 1258–1264.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Dyall R, Bowne WB, Weber LW, LeMaoult J, Szabo P, Moroi Y et al. Heterclitic immunization induces tumor immunity. J Exp Med 1998; 188: 1553–1561.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bowne WB, Srinivasan R, Wolchok JD, Hawkins WG, Blachere NE, Dyall R et al. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med 1999; 190: 1717–1722.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Bowne WB, Wolchok JD, Hawkins WG, Srinivasan R, Gregor P, Blachere NE et al. Injection of DNA encoding granulocyte-macrophage colong-stimulating factor recruits dendritic cells for immune adjuvant effects. Cytokines Cell Mol Ther 1999; 5: 217–225.

    CAS  PubMed  Google Scholar 

  15. Lewis JJ, Houghton AN . Definition of tumor antigens suitable for vaccine construction. Semin Cancer Biol 1995; 6: 321–327.

    CAS  PubMed  Google Scholar 

  16. Curtis SA, Cohen JV, Kluger HM . Evolving immunotherapy approaches for renal cell carcinoma. Curr Oncol Rep 2016; 18: 57.

    PubMed  Google Scholar 

  17. Smith HG, Hayes AJ . The role of regional chemotherapy in the management of extremity soft tissue malignancies. Eur J Surg Oncol 2016; 42: 7–17.

    CAS  PubMed  Google Scholar 

  18. Herzberg B, Fisher DE . Metastatic melanoma and immunotherapy. Clin Immunol 2016 (e-pub ahead of print 16 July 2016; doi:10.1016/j.clim.2016.0).

  19. Saied A, Pillarisetty VG, Katz SC . Immunotherapy for solid tumors—a review for surgeons. J Surg Res 2014; 187: 525–535.

    CAS  PubMed  Google Scholar 

  20. Mohkam K, Passot G, Cotte E, Bakrin N, François-Noël G, Stanislas L et al. Resectability of peritoneal carcinomatosis: learnings from a prospective cohort of 533 consecutive patients selected for cytoreductive surgery. Ann Surg Oncol 2016; 23: 1261–1270.

    PubMed  Google Scholar 

  21. Brink JA, Hany T. Pathways for the spread of disease in the abdomen. In: Hodler J, Kubik-Huch RA, von Schulthess GK, Zollikofer CL (eds). Disease of the Abdomen and Pelvis: Springer-Verlag Mailand, 2014, p 203–210..

  22. Sampson JA . Implantation peritoneal carcinomatosis of ovarian origin. Am J Pathol 1931; 7: 423–443.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Fidler IJ . The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003; 3: 453–458.

    CAS  PubMed  Google Scholar 

  24. Sugarbaker PH . Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology. Cancer Treat Res 1996; 82: 79–100.

    CAS  PubMed  Google Scholar 

  25. Rajeev R, Turaga KK . Hyperthermic intraperitoneal chemotherapy and cytoreductive surgery in the management of peritoneal carcinomatosis. Cancer Control 2016; 23: 36–46.

    PubMed  Google Scholar 

  26. Terzi C, Arslan NC, Canda AE . Peritoneal carcinomatosis of gastrointestinal tumors: where are we now? World J Gastroenterol 2014; 20: 14371–14380.

    PubMed  PubMed Central  Google Scholar 

  27. Jafari MD, Halabi WJ, Stamos MJ, Nguyen VQ, Carmichael JC, Mills SD et al. Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the american college of surgeons national surgical quality improvement program. JAMA Surg 2014; 149: 170–175.

    PubMed  Google Scholar 

  28. Sugarbaker PH . Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy. Tech Coloproctol 2005; 9: 95–103.

    CAS  PubMed  Google Scholar 

  29. Shariat-Madar B, Jayakrishnan TT, Gamblin TC, Turaga KK . Surgical management of bowel obstruction in patients with peritoneal carcinomatosis. J Surg Oncol 2014; 110: 666–669.

    PubMed  Google Scholar 

  30. Chu DZJ, Lang NP, Thompson C, Osteen PK, Westbrook KC . Peritoneal carcinomatosis in nongynecologic malignancy: a prospective study of prognostic factors. Cancer 1989; 63: 634–367.

    Google Scholar 

  31. Aranha GV, Folk FA, Greenlee HB . Surgical palliation of small bowel obstruction due to metastatic carcinoma. Am Surg 1981; 47: 99–102.

    CAS  PubMed  Google Scholar 

  32. Glass RL, LeDuc RJ . Small intestinal obstruction from peritoneal carcinomatosis. Am J Surg 1973; 125: 316–317.

    CAS  PubMed  Google Scholar 

  33. Kerscher AG, Chua TC, Gasser M, Maeder U, Kunzmann V, Isbert C et al. Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades. Br J Cancer 2013; 108: 1432–1439.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 2004; 22: 3284–3292.

    CAS  PubMed  Google Scholar 

  35. Dawson LE, Russell AH, Tong D, Wisbeck WM . Adenocarcinoma of the sigmoid colon: sites of initial dissemination and clinical patterns of recurrence following surgery alone. J Surg Oncol 1983; 22: 95–99.

    CAS  PubMed  Google Scholar 

  36. Van Oudheusden TR, Nienjuijs SW, Luyer MD, Nieuwenhuijzen GA, Lemmens VE, Rutten HJ et al. Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: a systematic review. Eur J Surg Oncol 2015; 41: 1269–1277.

    CAS  PubMed  Google Scholar 

  37. Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol 2012; 30: 2449–2456.

    PubMed  Google Scholar 

  38. Miner TJ, Shia J, Jaques DP, Klimstra DS, Brennan MF, Coit DG . Long-term survival following treatment of Pseudomyxoma peritonei. Ann Surg 2005; 241: 300–308.

    PubMed  PubMed Central  Google Scholar 

  39. Yu W, Whang I, Chung HY, Averbach A, Sugarbaker PH . Indications for early postoperative intraperitoneal chemotherapy of advanced gastric cancer: results of a prospective randomized trial. World J Surg 2001; 25: 985–990.

    CAS  PubMed  Google Scholar 

  40. Neuwirth MG, Alexander HR, Karakousis GC . Then and now: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), a historical perspective. J Gastrointest Oncol 2016; 7: 18–28.

    PubMed  PubMed Central  Google Scholar 

  41. Griffiths CT . Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. Natl Cancer Inst Monogr 1975; 42: 101–104.

    CAS  PubMed  Google Scholar 

  42. Long RT, Spratt JS, Dowling E . Pseudomyxoma Peritonei. New concepts in management with a report of seventeen patients. Am J Surg 1969; 117: 162–169.

    CAS  PubMed  Google Scholar 

  43. Ghosh BC, Huvos AG, Whiteley HW . Pseudomyxoma Peritonei. Dis Colon Rectum 1972; 15: 420–425.

    CAS  PubMed  Google Scholar 

  44. Spratt JS, Adcock RA, Sherrill W, Travathen S . Hyperthermic peritoneal perfusion system in canines. Cancer Res 1980; 40: 253–255.

    CAS  PubMed  Google Scholar 

  45. Pretorius RG, Petrilli ES, Kean CK, Ford LC, Hoeschele JD, Lagasse LD . Comparison of the IV and IP routes of administration of cisplatin in dogs. Cancer Treat Rep 1981; 65: 1055–1062.

    CAS  PubMed  Google Scholar 

  46. Spratt JS, Adcock RA, Muskovin M, Sherrill W, McKeown J . Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res 1980; 40: 256–260.

    CAS  PubMed  Google Scholar 

  47. Dedrick RL, Myers CE, Bungay PM, DeVita VT . Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 1978; 62: 1–11.

    CAS  PubMed  Google Scholar 

  48. Palta JR. Design and testing of a therapeutic infusion filtration system. M. S. thesis, University of Missouri, Columbia, Mo., 1977..

  49. Zimm S, Cleary SM, Lucas WE, Weiss RJ, Markman M, Andrews PA et al. Phase I/pharmacokinetic study of intraperitoneal cisplatin and etoposide. Cancer Res 1987; 47: 1712–1716.

    CAS  PubMed  Google Scholar 

  50. Sugarbaker PH, Gianola FJ, Speyer JC, Wesley R, Barofsky I, Meyers CE . Prospective, randomized trial of intravenous versus intraperitoneal 5-fluorouracil in patients with advanced primary colon or rectal cancer. Surgery 1985; 98: 414–422.

    CAS  PubMed  Google Scholar 

  51. Howell SB, Zimm S, Markman M, Abramson IS, Cleary S, Lucas WE et al. Long-term survival of advanced refractory ovarian carcinoma patients with small-volume disease treated with intraperitoneal chemotherapy. J Clin Oncol 1987; 5: 1607–1612.

    CAS  PubMed  Google Scholar 

  52. Sugarbaker PH . Peritonectomy procedures. Ann Surg 1995; 221: 29–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Alexander HR, Fraker DL . Treatment of peritoneal carcinomatosis by continuous hyperthermic peritoneal perfusion with cisplatin. Cancer Treat Res 1996; 81: 41–50.

    CAS  PubMed  Google Scholar 

  54. Bartlett DL, Buell JF, Libutti SK, Reed E, Lee KB, Figg WD et al. A phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis. Cancer 1998; 83: 1251–1261.

    CAS  PubMed  Google Scholar 

  55. Ma GY, Bartlett DL, Reed E, Figg WD, Lush RM, Lee KB et al. Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma. Cancer J Sci Am 1997; 3: 174–179.

    CAS  PubMed  Google Scholar 

  56. Portilla AG, Sugarbaker PH, Chang D . Second-look surgery after cytoreduction and intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer: analysis of prognostic features. World J Surg 1999; 23: 23–29.

    CAS  PubMed  Google Scholar 

  57. Network NCC. NCCN Guidelines Version 2.2016 Colon Cancer. Available from https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.

  58. Stutman O . Immunodepression and malignancy. Adv Cancer Res 1975; 22: 261–422.

    CAS  PubMed  Google Scholar 

  59. Steinman RM, Cohen ZA . Identification of a novel cell type in peripheral lymhoid organs of mice. J Exp Med 1973; 137: 1142–1162.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Steinman RM, Nussenzweig MC . Dendritic cells: features and functions. Immunol Rev 1980; 53: 127–147.

    CAS  PubMed  Google Scholar 

  61. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 5: 1485–1492.

    Google Scholar 

  62. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850–854.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–129.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Motzer RJ, Russo P . Systemic therapy for renal cell carcinoma. J Urol 2000; 163: 408–417.

    CAS  PubMed  Google Scholar 

  65. Gross JA, St John T, Allison JP . The murine homologue of the T lymphocyte antigen CD28. Molecular cloning and cell surface expression. J Immunol 1990; 144: 3201–3210.

    CAS  PubMed  Google Scholar 

  66. Krummel MF, Allison JP . CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995; 182: 459–465.

    CAS  PubMed  Google Scholar 

  67. Cozar JM, Romero JM, Aptsiauri N, Vazquez F, Vilchez JR, Tallada M et al. High incidence of CTLA-4 AA (CT60) polymorphism in renal cell cancer. Hum Immunol 2007; 68: 698–704.

    CAS  PubMed  Google Scholar 

  68. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H et al. Engagement of the Pd-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192: 1027–1034.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001; 2: 261–268.

    CAS  PubMed  Google Scholar 

  70. Zarour HM . Reversing T-cell dysfunction and exhaustion in cancer. Clin Cancer Res 2016; 22: 1856–1864.

    CAS  PubMed  PubMed Central  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: 1509–1518.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Porter DL, Levine BL, Kalos M, Bagg A, June CH . Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365: 725–733.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Katz SC, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res 2015; 21: 3149–3159.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 2011; 19: 620–626.

    CAS  PubMed  Google Scholar 

  75. Katz SC, Point GR, Cunetta M, Thorn M, Guha P, Espat NJ et al. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Ther 2016; 23: 142–148.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Burga RA, Thorn M, Point GR, Guha P, Nguyen CT, Licata LA et al. Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T. Cancer Immunol Immunother 2015; 64: 817–829.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Koneru M, Purdon TJ, Spriggs D, Koneru S, Brentjens RJ . IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. Oncoimmunology 2015; 4: e994446.

    PubMed  PubMed Central  Google Scholar 

  78. Hong H, Brown CE, Ostberg JR, Priceman SJ, Chang WC, Weng L et al. L1 cell adhesion molecule-specific chimeric antigen receptor-redirected human T cells exhibit specific and efficient antitumor activity against human ovarian cancer in mice. PLoS One 2016; 11: e0146885.

    PubMed  PubMed Central  Google Scholar 

  79. VanLith ML, Kohlgraf KG, Sivinski CL, Tempero RM, Hollingsworth MA . MUC1-specific antitumor responses: molecular requirements for CD4-mediated responses. Int Immunol 2002; 14: 873–882.

    CAS  PubMed  Google Scholar 

  80. Dobrzanski MJ, Rewers-Felkins KA, Quinlin IS, Samad KA, Phillips CA, Robinson W et al. Autologous MUC1-specific Th1 effector cell immunotherapy induces differential levels of systemic TReg cell subpopulations that result in increased ovarian cancer patient survival. Clin Immunol 2009; 133: 333–352.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Ma Z, Li W, Yoshiya S, Xu Y, Hata M, El-Darawish Y et al. Augmentation of immune checkpoint cancer immunotherapy with IL18. Clin Cancer Res 2016; 22: 2969–2980.

    CAS  PubMed  Google Scholar 

  82. Makkouk A, Weiner GJ . Cancer immunotherpay and breaking immune tolerance: new approaches to an old challenge. Cancer Res 2015; 75: 5–10.

    CAS  PubMed  Google Scholar 

  83. Le Mercier I, Lines JL, Noelle RJ . Beyond CTLA-4 and PD-1, the generation Z of negative checkpoint regulators. Front Immunol 2015; 6: 418.

    PubMed  PubMed Central  Google Scholar 

  84. Ai YQ, Cai K, Hu JH, Jiang LW, Gao YR, Zhao H et al. The clinical effects of dendritic cell vaccines combined with cytokine-induced killer cells intraperitoneal injected on patients with malignant ascites. Int J Clin Exp Med 2014; 7: 4272–4281.

    PubMed  PubMed Central  Google Scholar 

  85. Gujar S, Dielscneider R, Clements D, Helson E, Shmulevitz M, Marcato P et al. Multifaceted therapeutic targeting of ovarian peritoneal carcinomatosis through virus-induced immunomodulation. Mol Ther 2013; 21: 338–347.

    CAS  PubMed  Google Scholar 

  86. Gujar SA, Pan DA, Marcato P, Garant KA, Lee PW . Oncolytic virus initiated protective immunity against prostate cancer. Mol Ther 2011; 19: 797–804.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Gujar SA, Marcato P, Pan D, Lee PW . Reovirus virotherapy overrides tumor antigen presentation evasion and promotes protective antitumor immunity. Mol Cancer Ther 2010; 9: 2924–2933.

    CAS  PubMed  Google Scholar 

  88. Oyer JL, Pandey V, Igarashi RY, Somanchi SS, Zakari A, Solh M et al. Natural killer cells stimulated with PM21 particles expand and biodistribute in vivo: clinical implications for cancer treatment. Cytotherapy 2016; 18: 653–663.

    CAS  PubMed  Google Scholar 

  89. Denman CJ, Denyukov VV, Somanchi SS, Phatarpekar PV, Kopp LM, Johnson JL et al. Membrane-bound IL-21 promotoes sustained ex vivo proliferation of human natural killer cells. PLoS One 2012; 7: e30264.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Fujisaki H, Kakuda H, Shimasaki N, Imai C, Ma J, Lockey T et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res 2009; 69: 4010–4017.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Geller MA, Knorr DA, Hermanson DA, Pribyl L, Bendzick L, McCullar V et al. Intraperitoneal delivery of human natural killer cells for treatment of ovarian cancer in a mouse xenograft model. Cryotherapy 2013; 15: 1297–1306.

    CAS  Google Scholar 

  92. Berger C, Berger M, Arina A, Schreiber K, Hyjek E, Schietinger A et al. Safety and immunologic effects of IL-15 administration in nonhuman primates. Blood 2009; 114: 2417–2426.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Liang X, Luo M, Wei XW, Ma CC, Yang YH, Shao B et al. A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy. Oncotarget 2016 (e-pub ahead of print 11 July 2016; doi:10.18632/oncotarget.10537).

  94. Chen YL, Chang MC, Huang CY, Chiang YC, Lin HW, Chen CA et al. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response. Mol Oncol 2012; 6: 360–369.

    CAS  PubMed  Google Scholar 

  95. Seimetz D . Novel monoclonal antibodies for cancer treatment: the trifunctional antibody catumaxomab (removab®). J Cancer 2011; 2: 309–316.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Ruf P, Gires O, Jäger M, Fellinger K, Atz J, Lindhofer H . Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer. Br J Cancer 2007; 97: 315–321.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV et al. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer 2010; 127: 2209–2221.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Heiss MM, Ströhlein MA, Jäger M, Kimmig R, Burges A, Schoberth A et al. Immunotherapy of malignant ascites with trifunctional antibodies. Tumor Immunol 2005; 117: 435–443.

    CAS  Google Scholar 

  99. Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res 2007; 13: 3899–3905.

    CAS  PubMed  Google Scholar 

  100. Mackey JR, Venner PM . Malignant ascites: demographics, therapeutic effacy and predictors of survival. Can J Oncol 1996; 6: 474–480.

    CAS  PubMed  Google Scholar 

  101. Wimberger P, Gilet H, Gonschior AK, Heiss MM, Moehler M, Oskay-Oezcelik G et al. Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone. Ann Oncol 2012; 23: 1979–1985.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Ströhlein MA, Siegel R, Jäger M, Lindhofer H, Jauch KW, Heiss MM. Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 2009; 28: 18..

  103. Sadeghi B, Arvieux C, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE I multicentric prospective study. Cancer 2000; 88: 358–363.

    CAS  PubMed  Google Scholar 

  104. Bokemeyer C, Stein A, Ridwelski K, Atanackovic D, Arnold D, Woll E et al. A phase II study of catumaxomab administered intra- and postoperatively as part of a multimodal approach in primarily resectable gastric cancer. Gastric Cancer 2015; 18: 833–842.

    CAS  PubMed  Google Scholar 

  105. Goéré D, Gras-Chaput N, Aupérin A, Flament C, Mariette C, Glehen O et al. Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab. BMC Cancer 2014; 14: 148.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W B Bowne.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morano, W., Aggarwal, A., Love, P. et al. Intraperitoneal immunotherapy: historical perspectives and modern therapy. Cancer Gene Ther 23, 373–381 (2016). https://doi.org/10.1038/cgt.2016.49

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cgt.2016.49

This article is cited by

Search

Quick links