Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Lymphoma | Primary research

Development of transplantable B-cell lymphomas in the MHC-defined miniature swine model

Authors: Alec R. Andrews, Zhaohui Wang, Robert A. Wilkinson, Jay A. Fishman, David H. Sachs, Nalu Navarro-Alvarez, Christene A. Huang

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Establishment of transplantable tumors in clinically relevant large animals allows translational studies of novel cancer therapeutics.

Methods

Here we describe the establishment, characterization, and serial transplantation of a naturally occurring B-cell lymphoma derived from a unique, highly inbred sub-line of Massachusetts General Hospital (MGH) major histocompatibility complex (MHC)-defined miniature swine.

Results

The lymphoblastic cell line (LCL) originated from peripheral blood of a 2.5 year old female swine leukocyte antigen (SLA)dd-inbred miniature swine breeder demonstrating clinical signs of malignancy. Flow cytometric phenotypic analysis of subclones derived from the original cell line revealed surface markers commonly expressed in a B-cell lineage neoplasm. A subclone of the original LCL was transplanted into mildly-conditioned histocompatible miniature swine and immunocompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Tissue and blood samples harvested 2 weeks following subcutaneous and intravenous injection in a highly inbred SLAdd pig were cultured for tumor growth and phenotypic analysis before serial transfer into NSG mice. Evidence of tumor growth in vivo was found in all tumor cell recipients. In vitro growth characteristics and surface phenotype were comparable between the original and serially transplanted tumor cell lines.

Conclusions

These results indicate the feasibility of developing a large-animal transplantable tumor model using cells derived from spontaneously occurring hematologic malignancies within the highly inbred miniature swine herd.
Appendix
Available only for authorised users
Literature
1.
Lieu CH, Tan ACC, Leong S, Diamond JR, Eckhardt SG. From bench to bedside: lessons learned in translating preclinical studies in cancer drug development. J Natl Cancer Inst. 2013;105(19):1441–56.CrossRef
2.
Day CPP, Merlino G, Van Dyke T. Preclinical mouse cancer models: a maze of opportunities and challenges. Cell. 2015;163(1):39–53.CrossRef
3.
Na YSS, Ryu MHH, Yoo C, Lee JKK, Park JM, Lee CWW, et al. Establishment and characterization of patient-derived xenograft models of gastrointestinal stromal tumor resistant to standard tyrosine kinase inhibitors. Oncotarget. 2017;8(44):76712–21.CrossRef
4.
Cassidy JW, Caldas C, Bruna A. Maintaining tumor heterogeneity in patient-derived tumor xenografts. Cancer Res. 2015;75(15):2963–8.CrossRef
5.
Sachs DH, Leight G, Cone J, Schwarz S, Stuart L, Rosenberg S. Transplantation in miniature swine. I. Fixation of the major histocompatibility complex. Transplantation. 1976;22(6):559–67.CrossRef
6.
Cho PS, Lo DP, Wikiel KJ, Rowland HC, Coburn RC, McMorrow IM, et al. Establishment of transplantable porcine tumor cell lines derived from MHC-inbred miniature swine. Blood. 2007;110(12):3996–4004.CrossRef
7.
Duran-Struuck R, Cho PS, Teague AG, Fishman B, Fishman AS, Hanekamp JS, et al. Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias. Vet Immunol Immunopathol. 2010;135(3–4):243–56.CrossRef
8.
Duran-Struuck R, Matar AJ, Huang CA. Myeloid leukemias and virally induced lymphomas in miniature inbred swine: development of a large animal tumor model. Front Genet. 2015;6:332.CrossRef
9.
Mezrich JD, Haller GW, Arn JS, Houser SL, Madsen JC, Sachs DH. Histocompatible miniature swine: an inbred large-animal model. Transplantation. 2003;75(6):904–7.CrossRef
10.
Huang CA, Fuchimoto Y, Scheier-Dolberg R, Murphy MC, Neville DM, Sachs DH. Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. J Clin Invest. 2000;105(2):173–81.CrossRef
11.
Huang CA, Fuchimoto Y, Gleit ZL, Ericsson T, Griesemer A, Scheier-Dolberg R, et al. Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus. Blood. 2001;97(5):1467–73.CrossRef
12.
Plotzki E, Keller M, Ehlers B, Denner J. Immunological methods for the detection of porcine lymphotropic herpesviruses (PLHV). J Virol Methods. 2016;233:72–7.CrossRef
13.
Wang Z, Duran-Struuck R, Crepeau R, Matar A, Hanekamp I, Srinivasan S, et al. Development of a diphtheria toxin based antiporcine CD3 recombinant immunotoxin. Bioconjug Chem. 2011;22(10):2014–20.CrossRef
14.
Doucette K, Dor FJ, Wilkinson RA, Martin SI, Huang CA, Cooper DK, et al. Gene expression of porcine lymphotrophic herpesvirus-1 in miniature Swine with posttransplant lymphoproliferative disorder. Transplantation. 2007;83(1):87–90.CrossRef
15.
Cho PS, Mueller NJ, Cameron AM, Cina RA, Coburn RC, Hettiaratchy S, et al. Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model. Am J Transplant. 2004;4(8):1274–82.CrossRef
16.
Dor FJ, Doucette KE, Mueller NJ, Wilkinson RA, Bajwa JA, McMorrow IM, et al. Posttransplant lymphoproliferative disease after allogeneic transplantation of the spleen in miniature swine. Transplantation. 2004;78(2):286–91.CrossRef
17.
Matar AJ, Crepeau RL, Pathiraja V, Robson S, Fishman JA, Spitzer TR, et al. Effects of mobilization regimens in donors on outcomes of hematopoietic cell transplantation in miniature Swine. Comp Med. 2012;62(6):487–94.PubMedPubMedCentral
18.
Horner BM, Cina RA, Wikiel KJ, Lima B, Ghazi A, Lo DP, et al. Predictors of organ allograft tolerance following hematopoietic cell transplantation. Am J Transplant. 2006;6(12):2894–902.CrossRef
19.
Andervont HB, Dunn TB. Transplantation of spontaneous and induced hepatomas in inbred mice. J Natl Cancer Inst. 1952;13(2):455–503.PubMed
20.
Cook ES, Nutini LG, Fardon JC. Resistance to transplanted and spontaneous isologous tumors in inbred strains of mice. Acta Unio Int Contra Cancrum. 1964;20:1541–4.PubMed
21.
Kaleem Z, Zehnbauer BA, White G, Zutter MM. Lack of expression of surface immunoglobulin light chains in B-cell non-Hodgkin lymphomas. Am J Clin Pathol. 2000;113(3):399–405.CrossRef
22.
Li S, Eshleman JR, Borowitz MJ. Lack of surface immunoglobulin light chain expression by flow cytometric immunophenotyping can help diagnose peripheral B-cell lymphoma. Am J Clin Pathol. 2002;118(2):229–34.CrossRef
23.
Rimsza LM, Day WA, McGinn S, Pedata A, Natkunam Y, Warnke R, et al. Kappa and lambda light chain mRNA in situ hybridization compared to flow cytometry and immunohistochemistry in B cell lymphomas. Diagn Pathol. 2014;9:144.CrossRef
24.
Demurtas A, Accinelli G, Pacchioni D, Godio L, Novero D, Bussolati G, et al. Utility of flow cytometry immunophenotyping in fine-needle aspirate cytologic diagnosis of non-Hodgkin lymphoma: a series of 252 cases and review of the literature. Appl Immunohistochem Mol Morphol. 2010;18(4):311–22.CrossRef
25.
Chadalavada D, Adamson TW, Burnett JC, Chen RW, Rossi JJ. Irradiated compared with nonirradiated NSG mice for the development of a human B-cell lymphoma model. Comp Med. 2014;64(3):179–85.PubMedPubMedCentral
26.
Tahsili-Fahadan P, Rashidi A, Cimino PJ, Bucelli RC, Keyrouz SG. Neurologic manifestations of intravascular large B-cell lymphoma. Neurol Clin Pract. 2016;6(1):55–60.CrossRef
27.
Gill S, Herbert KE, Prince HM, Wolf MM, Wirth A, Ryan G, et al. Mantle cell lymphoma with central nervous system involvement: frequency and clinical features. Br J Haematol. 2009;147(1):83–8.CrossRef
28.
Hagemann UB, Wickstroem K, Wang E, Shea AO, Sponheim K, Karlsson J, et al. In vitro and in vivo efficacy of a novel CD33-targeted thorium-227 conjugate for the treatment of acute myeloid leukemia. Mol Cancer Ther. 2016;15(10):2422–31.CrossRef
29.
Burkina V, Rasmussen MK, Pilipenko N, Zamaratskaia G. Comparison of xenobiotic-metabolising human, porcine, rodent, and piscine cytochrome P450. Toxicology. 2017;375:10–27.CrossRef
30.
Park JS, Withers SS, Modiano JF, Kent MS, Chen M, Luna JI, et al. Canine cancer immunotherapy studies: linking mouse and human. J Immunother Cancer. 2016;4:97.CrossRef
31.
Roy J, Wycislo KL, Pondenis H, Fan TM, Das A. Comparative proteomic investigation of metastatic and non-metastatic osteosarcoma cells of human and canine origin. PLoS ONE. 2017;12(9):e0183930.CrossRef
32.
Basel MT, Balivada S, Beck AP, Kerrigan MA, Pyle MM, Dekkers JC, et al. Human xenografts are not rejected in a naturally occurring immunodeficient porcine line: a human tumor model in pigs. Biores Open Access. 2012;1(2):63–8.CrossRef
33.
Schook LB, Collares TV, Hu W, Liang Y, Rodrigues FM, Rund LA, et al. A genetic porcine model of cancer. PLoS ONE. 2015;10(7):e0128864.CrossRef
34.
Schachtschneider KM, Schwind RM, Newson J, Kinachtchouk N, Rizko M, Mendoza-Elias N, et al. The oncopig cancer model: an innovative large animal translational oncology platform. Front Oncol. 2017;7:190.CrossRef
35.
Schachtschneider KM, Schwind RM, Darfour-Oduro KA, De AK, Rund LA, Singh K, et al. A validated, transitional and translational porcine model of hepatocellular carcinoma. Oncotarget. 2017;8(38):63620–34.CrossRef
Metadata
Title
Development of transplantable B-cell lymphomas in the MHC-defined miniature swine model
Authors
Alec R. Andrews
Zhaohui Wang
Robert A. Wilkinson
Jay A. Fishman
David H. Sachs
Nalu Navarro-Alvarez
Christene A. Huang
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Lymphoma
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0954-3

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region

Primary research

Identification of a 6-gene signature predicting prognosis for colorectal cancer

Primary research

Overexpression of CD59 inhibits apoptosis of T-acute lymphoblastic leukemia via AKT/Notch1 signaling pathway

Primary research

Relationship between the upregulation of Notch1 signaling and the clinical characteristics of patients with papillary thyroid carcinoma in East Asia: a systematic review and meta-analysis

Primary research

Effect of Gallic acid in potentiating chemotherapeutic effect of Paclitaxel in HeLa cervical cancer cells

Primary research

Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits