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Molecular Targets for Antibody-Mediated Immunotherapy of Malignant Glioma

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CNS Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Despite advances in surgical and radiation therapy over the past two decades, the prognosis for many brain -tumor patients remains dismal. Novel antibody-mediated immunotherapeutics are emerging in the next generation of targeted therapeutic drugs for cancer treatment, and at least nine have been approved by the FDA to date. In this chapter we review the identification and validation of appropriate CNS tumor-associated antigens and the current status of antibody-mediated therapies under development and those that are already showing encouraging promise in the clinical setting.

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Abbreviations

AA:

anaplastic astrocytoma

BD:

boronated polyamidoamine dendrimer

CDC:

complement-dependent cytotoxicity

CDR:

complementarity-determining region

CSPG:

chondroitin sulfate proteoglycan

ds/scFv:

disulfide-linked scFv

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

EGFRvIII:

EGFR variant III

EGFRwt:

EGFR wild type

FNIII:

fibronectin type III

GBM:

glioblastoma multiforme

GPI:

glycosyl-phosphatidylinositol

GPNMB:

glycoprotein nonmetastatic melanoma protein B

Ig:

immunoglobulin

IV:

intravenous

mAb:

monoclonal antibody

MRP:

multidrug resistance protein

MTD:

maximum tolerated dose

NCAM:

neural cell adhesion molecule

PNET:

primitive neuroectodermal tumor

scFv:

single-chain variable-fragment antibody

SCRC:

surgically created resection cavity

SIP:

small immunoprotein

TMZ:

temozolomide

Tn-C:

tenascin-C

VEGF:

vascular endothelial growth factor

XRT:

radioimmunotherapy

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Acknowledgements

We would like to thank Paul Walker for reading this manuscript and providing constructive comments and feedback. Also, we thank Dr. Yukinari Kato for suggesting amendments to the section describing podoplanin. The research of Dr. Bigner is supported by NINDS Grant 5P50-NS20023-25, NIH Merit Award R37 CA 011898-38, NIH SPORE Grant 5P50 CA108786-4, and a Pediatric Brain Tumor Foundation Institute Grant. Darell D. Bigner is a paid consultant or receives royalties or holds stock in Amgen, Bradmer Pharmaceuticals, and Avant.

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Authors and Affiliations

  1. Department of Pathology, Duke University Medical Center, 181A Medical Sciences Research Building, 27710, Durham, NC, USA

    Joanne E. Ayriss

  2. Department of Pathology, Duke University Medical Center, 181C Medical Sciences Research Building, 27710, Durham, 3156, North Carolina

    Chien-Tsun Kuan

  3. Department of Surgery/Neuro-oncology, Duke University Medical CenterThe Preston Robert Tisch Brain Tumor Center, Room 047 Baker House, Trent Drive, 27710, Durham, 3624, North Carolina

    Susan T. Boulton

  4. Department of Surgery Department of Pediatrics, Duke University Medical Center The Preston Robert Tisch Brain Tumor Center, Room 047 Baker House, Trent Drive, 27710, Durham, 3624, North Carolina

    David A. Reardon

  5. Department of Pathology, Duke University Medical Center The Preston Robert Tisch Brain Tumor Center, 177 Medical Sciences Research Building, 27710, Durham, 3156, North Carolina

    Darell D. Bigner

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  1. Joanne E. Ayriss
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  2. Chien-Tsun Kuan
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  3. Susan T. Boulton
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  4. David A. Reardon
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  5. Darell D. Bigner
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Correspondence to Joanne E. Ayriss .

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  1. School of Medicine, Emory University, Clifton Road 1365C, Atlanta, 30322, U.S.A.

    Erwin G. Meir

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Ayriss, J.E., Kuan, CT., Boulton, S.T., Reardon, D.A., Bigner, D.D. (2009). Molecular Targets for Antibody-Mediated Immunotherapy of Malignant Glioma. In: Meir, E. (eds) CNS Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-553-8_36

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