Skip to main content
Top
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Hypothesis

Xenogeneic cell therapy provides a novel potential therapeutic option for cancers by restoring tissue function, repairing cancer wound and reviving anti-tumor immune responses

Authors: Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr

Published in: Cancer Cell International | Issue 1/2018

Login to get access

Abstract

Conventional cancer treatments such as surgery, radiotherapy, chemotherapy and targeted therapy, not only destruct tumors, but also injure the normal tissues, resulting in limited efficacy. Recent advances in cancer therapy have aimed at changing the host milieu of cancer against its development and progression by targeting tumor microenvironment and host immune system to eradicate tumors. To the host body, tumors arise in tissues. They impair the normal healthy tissue physiological function, become chronically inflamed and develop non-healing or overhealing wounds as well as drive immuno-suppressive activity to escape immunity attack. Therefore, the rational therapeutic strategies for cancers should treat both the tumors and the host body for the best efficacy to turn the deadly malignant disease to a manageable one. Xenogeneic cell therapy (i.e. cellular xenotransplantation) using cells from non-human source animals such as pigs has shown promising results in animal studies and clinical xenotransplantation in restoring lost tissue physiological function and repairing the wound. However, the major hurdle of xenogeneic cell therapy is the host immunological barriers that are induced by transplanted xenogeneic cells to reject xenografts. Possibly, the immunological barriers of xenogeneic cells could be used as immunological boosters to activate the host immune system. Here, we hypothesized that because of the biological properties of xenogeneic cells to the recipient humans, the transplantation of xenogeneic cells (i.e. cellular xenotransplantation) into cancer patients’ organs of the same origin with developed tumors may restore the impaired function of organs, repair the wound, reduce chronic inflammation and revive the anti-tumor immunity to achieve beneficial outcome for patients.
Literature
1.
2.
go back to reference Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411(6835):375–9.CrossRefPubMed Liotta LA, Kohn EC. The microenvironment of the tumour-host interface. Nature. 2001;411(6835):375–9.CrossRefPubMed
3.
go back to reference Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011;17(3):320–9.CrossRefPubMedPubMedCentral Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med. 2011;17(3):320–9.CrossRefPubMedPubMedCentral
4.
go back to reference Vasudev NS, Reynolds AR. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis. 2014;17(3):471–94.CrossRefPubMedPubMedCentral Vasudev NS, Reynolds AR. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions. Angiogenesis. 2014;17(3):471–94.CrossRefPubMedPubMedCentral
5.
go back to reference Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273–90.CrossRefPubMedPubMedCentral Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273–90.CrossRefPubMedPubMedCentral
6.
go back to reference Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–9.CrossRefPubMed Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–9.CrossRefPubMed
7.
go back to reference Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.CrossRefPubMed Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.CrossRefPubMed
8.
go back to reference Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA. 1985;254(23):3321–9.CrossRefPubMed Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA. 1985;254(23):3321–9.CrossRefPubMed
9.
go back to reference Starzl TE, Fung J, Tzakis A, Todo S, Demetris AJ, Marino IR, Doyle H, Zeevi A, Warty V, Michaels M, et al. Baboon-to-human liver transplantation. Lancet. 1993;341(8837):65–71.CrossRefPubMedPubMedCentral Starzl TE, Fung J, Tzakis A, Todo S, Demetris AJ, Marino IR, Doyle H, Zeevi A, Warty V, Michaels M, et al. Baboon-to-human liver transplantation. Lancet. 1993;341(8837):65–71.CrossRefPubMedPubMedCentral
10.
go back to reference Edge AS, Gosse ME, Dinsmore J. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Cell Transplant. 1998;7(6):525–39.CrossRefPubMed Edge AS, Gosse ME, Dinsmore J. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Cell Transplant. 1998;7(6):525–39.CrossRefPubMed
11.
go back to reference Nature America Inc. Xenotransplantation. Nat Biotechnol. 2000;18:IT53–55. Nature America Inc. Xenotransplantation. Nat Biotechnol. 2000;18:IT53–55.
12.
go back to reference Rood PP, Cooper DK. Islet xenotransplantation: are we really ready for clinical trials? Am J Transplant. 2006;6(6):1269–74.CrossRefPubMed Rood PP, Cooper DK. Islet xenotransplantation: are we really ready for clinical trials? Am J Transplant. 2006;6(6):1269–74.CrossRefPubMed
13.
go back to reference Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, et al. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science. 2003;299(5605):411–4.CrossRefPubMed Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, et al. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science. 2003;299(5605):411–4.CrossRefPubMed
14.
go back to reference Kolber-Simonds D, Lai L, Watt SR, Denaro M, Arn S, Augenstein ML, Betthauser J, Carter DB, Greenstein JL, Hao Y, et al. Production of alpha-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci USA. 2004;101(19):7335–40.CrossRefPubMedPubMedCentral Kolber-Simonds D, Lai L, Watt SR, Denaro M, Arn S, Augenstein ML, Betthauser J, Carter DB, Greenstein JL, Hao Y, et al. Production of alpha-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci USA. 2004;101(19):7335–40.CrossRefPubMedPubMedCentral
15.
go back to reference Reyes LM, Estrada JL, Wang ZY, Blosser RJ, Smith RF, Sidner RA, Paris LL, Blankenship RL, Ray CN, Miner AC, et al. Creating class I MHC-null pigs using guide RNA and the Cas9 endonuclease. J Immunol. 2014;193(11):5751–7.CrossRefPubMed Reyes LM, Estrada JL, Wang ZY, Blosser RJ, Smith RF, Sidner RA, Paris LL, Blankenship RL, Ray CN, Miner AC, et al. Creating class I MHC-null pigs using guide RNA and the Cas9 endonuclease. J Immunol. 2014;193(11):5751–7.CrossRefPubMed
16.
go back to reference Gao H, Zhao C, Xiang X, Li Y, Zhao Y, Li Z, Pan D, Dai Y, Hara H, Cooper DK, et al. Production of alpha1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-deficient pigs by CRISPR/Cas9 and handmade cloning. J Reprod Dev. 2017;63(1):17–26.CrossRefPubMed Gao H, Zhao C, Xiang X, Li Y, Zhao Y, Li Z, Pan D, Dai Y, Hara H, Cooper DK, et al. Production of alpha1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-deficient pigs by CRISPR/Cas9 and handmade cloning. J Reprod Dev. 2017;63(1):17–26.CrossRefPubMed
17.
go back to reference Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol. 2007;7(7):519–31.CrossRefPubMed Yang YG, Sykes M. Xenotransplantation: current status and a perspective on the future. Nat Rev Immunol. 2007;7(7):519–31.CrossRefPubMed
18.
go back to reference Cardona K, Korbutt GS, Milas Z, Lyon J, Cano J, Jiang W, Bello-Laborn H, Hacquoil B, Strobert E, Gangappa S, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12(3):304–6.CrossRefPubMed Cardona K, Korbutt GS, Milas Z, Lyon J, Cano J, Jiang W, Bello-Laborn H, Hacquoil B, Strobert E, Gangappa S, et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med. 2006;12(3):304–6.CrossRefPubMed
19.
go back to reference Hering BJ, Wijkstrom M, Graham ML, Hardstedt M, Aasheim TC, Jie T, Ansite JD, Nakano M, Cheng J, Li W, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006;12(3):301–3.CrossRefPubMed Hering BJ, Wijkstrom M, Graham ML, Hardstedt M, Aasheim TC, Jie T, Ansite JD, Nakano M, Cheng J, Li W, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med. 2006;12(3):301–3.CrossRefPubMed
20.
go back to reference Fink JS, Schumacher JM, Ellias SL, Palmer EP, Saint-Hilaire M, Shannon K, Penn R, Starr P, VanHorne C, Kott HS, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: preliminary results. Cell Transplant. 2000;9(2):273–8.CrossRefPubMed Fink JS, Schumacher JM, Ellias SL, Palmer EP, Saint-Hilaire M, Shannon K, Penn R, Starr P, VanHorne C, Kott HS, et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: preliminary results. Cell Transplant. 2000;9(2):273–8.CrossRefPubMed
21.
24.
25.
26.
go back to reference Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.CrossRefPubMed Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.CrossRefPubMed
28.
29.
go back to reference Nilsson B. The instant blood-mediated inflammatory reaction in xenogeneic islet transplantation. Xenotransplantation. 2008;15(2):96–8.CrossRefPubMed Nilsson B. The instant blood-mediated inflammatory reaction in xenogeneic islet transplantation. Xenotransplantation. 2008;15(2):96–8.CrossRefPubMed
30.
go back to reference Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707–23.CrossRefPubMed Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707–23.CrossRefPubMed
31.
go back to reference Abdel-Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS ONE. 2016;11(7):e0160221.CrossRefPubMedPubMedCentral Abdel-Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with cancer: a systematic review of case reports. PLoS ONE. 2016;11(7):e0160221.CrossRefPubMedPubMedCentral
32.
33.
go back to reference Garkavenko O, Emerich DF, Muzina M, Muzina Z, Vasconcellos AV, Ferguson AB, Cooper IJ, Elliott RB. Xenotransplantation of neonatal porcine liver cells. Transplant Proc. 2005;37(1):477–80.CrossRefPubMed Garkavenko O, Emerich DF, Muzina M, Muzina Z, Vasconcellos AV, Ferguson AB, Cooper IJ, Elliott RB. Xenotransplantation of neonatal porcine liver cells. Transplant Proc. 2005;37(1):477–80.CrossRefPubMed
34.
go back to reference Matsumoto S, Abalovich A, Wechsler C, Wynyard S, Elliott RB. Clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes. EBioMedicine. 2016;12:255–62.CrossRefPubMedPubMedCentral Matsumoto S, Abalovich A, Wechsler C, Wynyard S, Elliott RB. Clinical benefit of islet xenotransplantation for the treatment of type 1 diabetes. EBioMedicine. 2016;12:255–62.CrossRefPubMedPubMedCentral
35.
go back to reference Vivarelli M, Bellusci R, Cucchetti A, Cavrini G, De Ruvo N, Aden AA, La Barba G, Brillanti S, Cavallari A. Low recurrence rate of hepatocellular carcinoma after liver transplantation: better patient selection or lower immunosuppression? Transplantation. 2002;74(12):1746–51.CrossRefPubMed Vivarelli M, Bellusci R, Cucchetti A, Cavrini G, De Ruvo N, Aden AA, La Barba G, Brillanti S, Cavallari A. Low recurrence rate of hepatocellular carcinoma after liver transplantation: better patient selection or lower immunosuppression? Transplantation. 2002;74(12):1746–51.CrossRefPubMed
Metadata
Title
Xenogeneic cell therapy provides a novel potential therapeutic option for cancers by restoring tissue function, repairing cancer wound and reviving anti-tumor immune responses
Authors
Chi-Ping Huang
Chi-Cheng Chen
Chih-Rong Shyr
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0501-7

Other articles of this Issue 1/2018

Cancer Cell International 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine