Abstract
In vivo modeling of cancer is a critical step in testing novel therapeutic strategies to advance patient care. Here we describe how to develop a humanized patient-derived xenograft (PDX) model of ovarian cancer that uses orthotopically transplanted patient ovarian tumors with autologous transfer of expanded tumor infiltrating T cells (TILs) as a model that can be utilized to test immunomodulating therapeutics in vivo.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Krisnawan VE, Stanley JA, Schwarz JK, DeNardo DG (2020) Tumor microenvironment as a regulator of radiation therapy: new insights into stromal-mediated radioresistance. Cancers (Basel) 12(10):2916. https://doi.org/10.3390/cancers12102916
Hirata E, Sahai E (2017) Tumor microenvironment and differential responses to therapy. Cold Spring Harb Perspect Med 7(7):a026781. https://doi.org/10.1101/cshperspect.a026781
Anderson NM, Simon MC (2020) The tumor microenvironment. Curr Biol 30(16):R921–R925. https://doi.org/10.1016/j.cub.2020.06.081
Mak IW, Evaniew N, Ghert M (2014) Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6(2):114–118
Maniati E, Berlato C, Gopinathan G, Heath O, Kotantaki P, Lakhani A, McDermott J, Pegrum C, Delaine-Smith RM, Pearce OMT, Hirani P, Joy JD, Szabova L, Perets R, Sansom OJ, Drapkin R, Bailey P, Balkwill FR (2020) Mouse ovarian cancer models recapitulate the human tumor microenvironment and patient response to treatment. Cell Rep 30(2):525–540.e7. https://doi.org/10.1016/j.celrep.2019.12.034
Gitto SB, Powell DJ Jr (2020) Of mice and men: pre-clinical models to identify therapy responsive patient subgroups. Gynecol Pelvic Med 3
Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172(5):2731–2738. https://doi.org/10.4049/jimmunol.172.5.2731
Domcke S, Sinha R, Levine DA, Sander C, Schultz N (2013) Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun 4:2126. https://doi.org/10.1038/ncomms3126
George E, Kim H, Krepler C, Wenz B, Makvandi M, Tanyi JL, Brown E, Zhang R, Brafford P, Jean S, Mach RH, Lu Y, Mills GB, Herlyn M, Morgan M, Zhang X, Soslow R, Drapkin R, Johnson N, Zheng Y, Cotsarelis G, Nathanson KL, Simpkins F (2017) A patient-derived-xenograft platform to study BRCA-deficient ovarian cancers. JCI Insight 2(1):e89760. https://doi.org/10.1172/jci.insight.89760
Lai Y, Wei X, Lin S, Qin L, Cheng L, Li P (2017) Current status and perspectives of patient-derived xenograft models in cancer research. J Hematol Oncol 10(1):106. https://doi.org/10.1186/s13045-017-0470-7
Liu JF, Palakurthi S, Zeng Q, Zhou S, Ivanova E, Huang W, Zervantonakis IK, Selfors LM, Shen Y, Pritchard CC, Zheng M, Adleff V, Papp E, Piao H, Novak M, Fotheringham S, Wulf GM, English J, Kirschmeier PT, Velculescu VE, Paweletz C, Mills GB, Livingston DM, Brugge JS, Matulonis UA, Drapkin R (2017) Establishment of patient-derived tumor xenograft models of epithelial ovarian Cancer for preclinical evaluation of novel therapeutics. Clin Cancer Res 23(5):1263–1273. https://doi.org/10.1158/1078-0432.CCR-16-1237
Owonikoko TK, Zhang G, Kim HS, Stinson RM, Bechara R, Zhang C, Chen Z, Saba NF, Pakkala S, Pillai R, Deng X, Sun SY, Rossi MR, Sica GL, Ramalingam SS, Khuri FR (2016) Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer. J Transl Med 14(1):111. https://doi.org/10.1186/s12967-016-0861-5
Kim HR, Kang HN, Shim HS, Kim EY, Kim J, Kim DJ, Lee JG, Lee CY, Hong MH, Kim SM, Kim H, Pyo KH, Yun MR, Park HJ, Han JY, Youn HA, Ahn MJ, Paik S, Kim TM, Cho BC (2017) Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Ann Oncol 28(6):1250–1259. https://doi.org/10.1093/annonc/mdx098
De La Rochere P, Guil-Luna S, Decaudin D, Azar G, Sidhu SS, Piaggio E (2018) Humanized mice for the study of immuno-oncology. Trends Immunol 39(9):748–763. https://doi.org/10.1016/j.it.2018.07.001
King MA, Covassin L, Brehm MA, Racki W, Pearson T, Leif J, Laning J, Fodor W, Foreman O, Burzenski L, Chase TH, Gott B, Rossini AA, Bortell R, Shultz LD, Greiner DL (2009) Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol 157(1):104–118. https://doi.org/10.1111/j.1365-2249.2009.03933.x
Drake AC, Chen Q, Chen J (2012) Engineering humanized mice for improved hematopoietic reconstitution. Cell Mol Immunol 9(3):215–224. https://doi.org/10.1038/cmi.2012.6
Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, Ito R, Ito M, Minegishi M, Minegishi N, Tsuchiya S, Sugamura K (2009) The analysis of the functions of human B and T cells in humanized NOD/shi-scid/gammac(null) (NOG) mice (hu-HSC NOG mice). Int Immunol 21(7):843–858. https://doi.org/10.1093/intimm/dxp050
Tanaskovic O, Verga Falzacappa MV, Pelicci PG (2019) Human cord blood (hCB)-CD34+ humanized mice fail to reject human acute myeloid leukemia cells. PLoS One 14(9):e0217345. https://doi.org/10.1371/journal.pone.0217345
Gitto SB, Kim H, Rafail S, Omran DK, Medvedev S, Kinose Y, Rodriguez-Garcia A, Flowers AJ, Xu H, Schwartz LE, Powell DJ Jr, Simpkins F (2020) An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer. Gynecol Oncol 156(1):222–232. https://doi.org/10.1016/j.ygyno.2019.10.011
Kim H, Xu H, George E, Hallberg D, Kumar S, Jagannathan V, Medvedev S, Kinose Y, Devins K, Verma P, Ly K, Wang Y, Greenberg RA, Schwartz L, Johnson N, Scharpf RB, Mills GB, Zhang R, Velculescu VE, Brown EJ, Simpkins F (2020) Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models. Nat Commun 11(1):3726. https://doi.org/10.1038/s41467-020-17127-2
Nakayama N, Nakayama K, Shamima Y, Ishikawa M, Katagiri A, Iida K, Miyazaki K (2010) Gene amplification CCNE1 is related to poor survival and potential therapeutic target in ovarian cancer. Cancer 116(11):2621–2634. https://doi.org/10.1002/cncr.24987
Acknowledgments
Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number TL1TR001880. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was awarded to S.B.G. from the Ovarian Cancer Research Alliance and the Rivkin Center for Ovarian Cancer.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Gitto, S.B., George, E., Medvedev, S., Simpkins, F., Powell, D.J. (2022). Humanized Patient-Derived Xenograft Models of Ovarian Cancer. In: Kreeger, P.K. (eds) Ovarian Cancer. Methods in Molecular Biology, vol 2424. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1956-8_17
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1956-8_17
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1955-1
Online ISBN: 978-1-0716-1956-8
eBook Packages: Springer Protocols