Xenograft Mouse Models for Tumour Targeting

  • Surinder K. SharmaEmail author
  • R Barbara Pedley
Part of the Springer Protocols Handbooks book series (SPH)


Monoclonal antibodies against tumour-associated antigens have been widely used for targetted therapy of cancer. Most of the pre-clinical assessment of efficacy and toxicity of these agents is carried out in immunodeficient mice xenografted with human tumours. Quantitative biodistribution is routinely assessed by administration of radiolabelled antibodies, followed by counting of radioactivity in tumour and normal tissues. However, in order to optimise the therapy design and synergistic combination of agents, it is desirable to understand the complex antibody-tumour interactions in-vivo and determine which regions of tumours are being targetted. This is achieved by quantitative, high resolution fluorescence microscopy, which can be employed to demonstrate the distribution and therapeutic efficacy of the targetting antibody in relation to the tumour microenvironment.


LS174T Cell PD10 Column Welwyn Garden City Green Needle Radiolabelled Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Dr Ethaar El-Emir for skillful technical assistance and Cancer Research UK and European Union FP7 (201342-ADAMANT) for grant support.


  1. Carter PJ (2006) Potent antibody therapeutics by design. Nat Rev Immunol 6:343–357PubMedCrossRefGoogle Scholar
  2. Carter PJ, Senter PD (2008) Antibody-drug conjugates for cancer therapy. Cancer J 14:154–169PubMedCrossRefGoogle Scholar
  3. Chari RV (2008) Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res 41:98–107PubMedCrossRefGoogle Scholar
  4. El-Emir E, Qureshi U, Dearling JL, Boxer GM, Clatworthy I, Folarin AA, Robson MP, Nagl S, Konerding MA, Pedley RB (2007) Predicting response to radioimmunotherapy from the tumor microenvironment of colorectal carcinomas. Cancer Res 67:11896–11905PubMedCrossRefGoogle Scholar
  5. Fidarova EF, El-Emir E, Boxer GM, Qureshi U, Dearling JL, Robson MP, Begent RH, Trott KR, Pedley RB (2008) Microdistribution of targeted, fluorescently labeled anti-carcinoembryonic antigen antibody in metastatic colorectal cancer: implications for radioimmunotherapy. Clin Cancer Res 14:2639–2646PubMedCrossRefGoogle Scholar
  6. Friedman M, Stahl S (2009) Engineered affinity proteins for tumour-targeting applications. Biotechnol Appl Biochem 53:1–29PubMedCrossRefGoogle Scholar
  7. Holliger P, Hudson PJ (2005) Engineered antibody fragments and the rise of single domains. Nat Biotechnol 23:1126–1136PubMedCrossRefGoogle Scholar
  8. Ojima I (2008) Guided molecular missiles for tumor-targeting chemotherapy–case studies using the second-generation taxoids as warheads. Acc Chem Res 41:108–119PubMedCrossRefGoogle Scholar
  9. Pedley RB, El-Emir E, Flynn AA, Boxer GM, Dearling J, Raleigh JA, Hill SA, Stuart S, Motha R, Begent RH (2002) Synergy between vascular targeting agents and antibody-directed therapy. Int J Radiat Oncol Biol Phys 54:1524–1531PubMedCrossRefGoogle Scholar
  10. Pedley RB, Hill SA, Boxer GM, Flynn AA, Boden R, Watson R, Dearling J, Chaplin DJ, Begent RH (2008) Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate. Cancer Res 61:4716–4722Google Scholar
  11. Raleigh JA, Calkins-Adams DP, Rinker LH, Ballenger CA, Weissler MC, Fowler WC Jr, Novotny DB, Varia MA (1998) Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res 58:3765–3768PubMedGoogle Scholar
  12. Sausville EA, Burger AM (2006) Contributions of human tumor xenografts to anticancer drug development. Cancer Res 66:3351–3354 discussionPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.UCL Cancer InstituteUniversity College LondonLondonUK

Personalised recommendations