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Antibody-Based Targeting of Tumor Vasculature and Stroma

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Tumor-Associated Fibroblasts and their Matrix

Part of the book series: The Tumor Microenvironment ((TTME,volume 4))

Abstract

Conventional cytotoxic therapies of cancer often suffer from a lack of specificity, leading to a poor therapeutic index and toxicities to normal organs. The targeted delivery of bioactive molecules (cytokines, radionuclides, drugs, photosensitizer, etc.) by means of an antibody specific to tumor-associated markers of the tumor stroma and endothelium offers an elegant way to overcome these drawbacks. In fact, tumor markers of the endothelium and extracellular matrix are particularly attractive, because of their accessibility for intravenously administered agents, their genomic stability and the various therapeutic options they offer, ranging from direct tumor cell killing, to tumor infarction and to the recruitment of immune cells.

In this chapter, we will review therapeutic strategies and concepts for antibody-based pharmacodelivery applications based on target proteins located in the subendothelial extracellular matrix. We also describe methodologies for the discovery of novel tumor markers and outline the advances in preclinical and clinical development of vascular targeting agents for cancer therapy.

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Abbreviations

CDR:

Complementarity determining region

EDA:

Extra-domain A of fibronectin

EDB:

Extra-domain B of fibronectin

EGF:

Epidermal growth factor

IgG:

Immunoglobulin G

PDT:

Photodynamic therapy

RIT:

Radioimmunotherapy

SAGE:

Serial analysis of gene expression

scFv:

Single-chain Fragment variable

SIP:

Small immunoprotein

TEM:

Tumor endothelial marker

PET:

Positron emission tomography

SPECT:

Single photon emission computed tomography

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

IFN:

Interferon

IL-2, -12, -15:

Interleukin-2, -12, -15

TNF:

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093, Zurich, Switzerland

    Katharina Frey & Dario Neri

Authors
  1. Katharina Frey
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  2. Dario Neri
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Correspondence to Katharina Frey or Dario Neri .

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  1. Siederstrasse 13, Villingen-Schwenningen, 78054, Germany

    Margareta M. Mueller

  2. Am Pferchelhang 32, Heidelberg, 69118, Germany

    Norbert E. Fusenig

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Frey, K., Neri, D. (2011). Antibody-Based Targeting of Tumor Vasculature and Stroma. In: Mueller, M., Fusenig, N. (eds) Tumor-Associated Fibroblasts and their Matrix. The Tumor Microenvironment, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0659-0_22

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