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Lessons learned from cancer vaccine trials and target antigen choice

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A wide variety of tumor antigens have been targeted in cancer immunotherapy studies. Traditionally, the focus has been on commonly overexpressed antigens shared across many patients and/or tumor types. As the field has progressed, the identity of human tumor rejection antigens has broadened. Immunologic monitoring of clinical trials has slowly elucidated candidate biomarkers of immune response and clinical response, and conversely, of immune dysfunction and suppression. We have utilized MART-1/Melan-A in our melanoma studies and observed a high frequency of immune responses and several significant clinical responses in patients vaccinated with this melanosomal protein. Alpha-fetoprotein is a shared, overexpressed tumor antigen and secreted glycoprotein that we have tested in hepatocellular cancer vaccines. Our recent studies have identified immunosuppressive and immune-skewing activities of this antigen. The choice of target antigen and its form can have unexpected effects.

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Abbreviations

AdV:

Adenovirus

AFP:

Alpha-fetoprotein

CEA:

Carcinoembryonic antigen

DC:

Dendritic cells

EGFR:

Epidermal growth factor receptor

HCC:

Hepatocellular cancer

HPV:

Human papilloma virus

LMW:

Low molecular weight

MAGE-A1:

Melanoma antigen family A1

MART-1:

Melanoma antigen recognized by T cells (aka Melan-A)

nAFP:

Cord blood-derived normal alpha-fetoprotein

NK:

Natural killer

OFA:

Oncofetal antigen

PGE2 :

Prostaglandin E2

TAA:

Tumor-associated antigen

tAFP:

Tumor-derived alpha-fetoprotein

TIL:

Tumor-infiltrating lymphocytes

Treg:

Regulatory T cells

TSA:

Tumor-specific antigen

WT-1:

Wilm’s tumor-1

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Acknowledgments

This work was supported by University of Pittsburgh Skin SPORE/National Institutes of Health Grant P50 CA121973; National Institutes of Health R01 Grant CA104524; and National Institutes of Health R01 Grant CA138635. This project used the University of Pittsburgh Cancer Institute Immunologic Monitoring and Cellular Products Laboratory shared resource (Lisa H. Butterfield, Director) that is supported in part by National Institutes of Health Grant award P30CA047904. The author acknowledges the support of Melanoma Program colleagues Dr. John M. Kirkwood, Dr. Ahmad A. Tarhini, and Dr. Hussein Tawbi in the current melanoma clinical studies. The author also thanks the current and recent members of the Butterfield research laboratory (Lazar Vujanovic, Patricia Santos, and Angela D. Pardee).

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Authors and Affiliations

  1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Lisa H. Butterfield

  2. Departments of Medicine, Surgery and Immunology, Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA, 15213, USA

    Lisa H. Butterfield

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  1. Lisa H. Butterfield
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Correspondence to Lisa H. Butterfield.

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Conflict of interest

Lisa H. Butterfield is co-inventor of patents covering aspects of alpha-fetoprotein as a target for T cell-mediated anti-hepatocellular cancer immunity.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Fourth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2015), held in Ljubljana, Slovenia, 27th–30th April 2015. It is part of a series of Focussed Research Reviews and meeting report in Cancer Immunology, Immunotherapy.

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Butterfield, L.H. Lessons learned from cancer vaccine trials and target antigen choice. Cancer Immunol Immunother 65, 805–812 (2016). https://doi.org/10.1007/s00262-016-1801-1

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