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Targeting tumor vasculature: expanding the potential of DNA cancer vaccines

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

Abstract

Targeting the tumor vasculature with anti-angiogenesis modalities is a bona fide validated approach that has complemented cancer treatment paradigms. Tumor vasculature antigens (TVA) can be immunologically targeted and offers multiple theoretical advantages that may enhance existing strategies against cancer. We focused on tumor endothelial marker 1 (TEM1/CD248) as a model TVA since it is broadly expressed on many different cancers. Our DNA-based vaccine approach demonstrated that CD248 can be effectively targeted immunologically; anti-tumor responses were generated in several mouse models; and CD8+/CD4+ T cell responses were elicited against peptides derived from CD248 protein. Our work supports our contention that CD248 is a novel immunotherapeutic target for cancer treatment and highlights the efficient, safe and translatable use of DNA-based immunotherapy. We next briefly highlight ongoing investigations targeting CD248 with antibodies as a diagnostic imaging agent and as a therapeutic antibody in an early clinical trial. The optimal approach for generating effective DNA-based cancer vaccines for several tumor types may be a combinatorial approach that enhances immunogenicity such as combination with chemotherapy. Additional combination approaches are discussed and include those that alleviate the immunosuppressive tumor microenvironment induced by myeloid-derived suppressor cells and T regulatory cells. Targeting the tumor vasculature by CD248-based immunological modalities expands the armamentarium against cancer.

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Abbreviations

ACT:

Adoptive cell therapy

ALL:

Acute lymphocytic leukemia

APC:

Antigen-presenting cells

bFGF:

Basic fibroblast growth factor

CAIX:

Carbonic anhydrase IX

CAR:

Chimeric antigen receptor

CLL:

Chronic lymphocytic leukemia

CTL:

Cytotoxic T lymphocytes

CXCL:

Chemokine (C-X-C motif) ligand

DC:

Dendritic cells

E2:

17β-estradiol

EC:

Endothelial cells

EPC:

Endothelial progenitor cells

G-CSF:

Granulocyte colony-stimulating factor

HGF:

Hepatocyte growth factor

IFN:

Interferon

IL:

Interleukin

IMG:

Intussusceptive microvascular growth

MDSC:

Myeloid-derived suppressor cells

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinases

PDGF:

Platelet-derived growth factor

scFv:

Single-chain antibody

TAA:

Tumor-associated antigen

TCR:

T cell receptor

TEM:

Tumor endothelial marker

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

Treg:

T regulatory lymphocytes

TT:

Tetanus toxoid

TVA:

Tumor vasculature antigen

VDA:

Vascular-disrupting agents

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgments

Financial support for A.F. is from the Basser Research Center for BRCA (Breast Cancer early onset) at Abramson Cancer Center, University of Pennsylvania; the Alliance for Cancer Gene Therapy, the National Institutes of Health (NIH) Director’s New Innovator Award (1DP2OD008514), and the Pennsylvania Department of Health (4100051725). The Italian Association for Cancer Research (AIRC) supported Stefano Ugel with Fellowship for studies abroad (2010).

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    Authors and Affiliations

    1. Ovarian Cancer Research Center (OCRC), University of Pennsylvania School of Medicine, Biomedical Research Building II/III, 13th Floor, 421 Curie Blvd., Philadelphia, PA, 19104, USA

      Stefano Ugel, John G. Facciponte, Francesco De Sanctis & Andrea Facciabene

    2. Immunology Section, Department of Pathology and Diagnostics, University of Verona, 37134, Verona, Italy

      Stefano Ugel & Francesco De Sanctis

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    1. Stefano Ugel
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    Correspondence to Andrea Facciabene.

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    This paper is a Focussed Research Review based on a presentation given at the Fourteenth International Conference on Progress in Vaccination against Cancer (PIVAC 14), held in Rome, Italy, 24th–26th September, 2014. It is part of a Cancer Immunology, Immunotherapy series of Focussed Research Reviews and meeting report.

    Stefano Ugel and John G. Facciponte have contributed equally to this paper.

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    Ugel, S., Facciponte, J.G., De Sanctis, F. et al. Targeting tumor vasculature: expanding the potential of DNA cancer vaccines. Cancer Immunol Immunother 64, 1339–1348 (2015). https://doi.org/10.1007/s00262-015-1747-8

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