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Tumor Antigen-Specific Monoclonal Antibody-Based Immunotherapy, Cancer Initiating Cells and Disease Recurrence

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Resistance to Immunotherapeutic Antibodies in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 2))

Abstract

Immunotherapy with tumor antigen (TA)-specific monoclonal antibody (mAb) has been shown to be effective in the treatment of several types of cancer. However, its efficacy is limited by the lack of response in some of the treated patients and by disease recurrence. In this chapter, following a short description of the characteristics of cancer initiating cells (CICs) and the markers used for their identification in various types of cancer, we will provide in vitro evidence to suggest that disease recurrence is caused by the lack of eradication of CICs by the TA-specific mAb-based immunotherapy. In addition, we will describe potential strategies to overcome this resistance mechanism which is a major obstacle to the successful application of TA-specific mAb-based immunotherapy.

Yangyang Wang and Francesco Sabbatino equally contributed to this manuscript.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

ALDH:

Aldeyde dehydrogenase

BAAA:

BODIPY™-aminoacetaldehyde

CDC:

Complement-dependent cytotoxicity

CICs:

Cancer initiating cells

CSPG4:

Chondroitin sulfate proteoglycan 4

CTL:

Cytotoxic T cells

DEAB:

Diethylaminobenzaldehyde

Grp94:

Glucose-regulated protein of 94 kDa

HSP:

Heat shock protein

mAb:

Monoclonal antibody

MCSP:

Melanoma-associated chondroitin sulfate proteoglycan

MDSC:

Myeloid-derived suppressor cells

MFI:

Mean fluorescence intensity

NG2:

Neuron-glial antigen 2

PDAC:

Pancreas ductal adenocarcinoma

SCID:

Severe combined immunodeficiency

SHH:

Sonic Hedgehog Homologue

T regs:

T regulatory cells

TA:

Tumor antigen

TNBC:

Triple negative breast cancer

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Acknowledgments

This work was supported by PHS grants RO1CA138188 and RO1CA110249 awarded by the National Cancer Institute and Susan Komen Post Doctoral Fellowship KG111486 awarded by the Susan G. Komen for the Cure Foundation.

Conflicts of Interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Yangyang Wang, Francesco Sabbatino, Ling Yu, Elvira Favoino, Xinhui Wang, Matteo Ligorio, Soldano Ferrone & Cristina R. Ferrone

  2. Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, USA

    Joseph H. Schwab

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  1. Yangyang Wang
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  2. Francesco Sabbatino
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  1. Molecular Genetics, University of California, Los Angeles Dept. Microbiology, Immunology &, Los Angeles, California, USA

    Benjamin Bonavida

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Wang, Y. et al. (2013). Tumor Antigen-Specific Monoclonal Antibody-Based Immunotherapy, Cancer Initiating Cells and Disease Recurrence. In: Bonavida, B. (eds) Resistance to Immunotherapeutic Antibodies in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7654-2_2

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