Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts

Jaewoo Lee, Martin Fassnacht, Smita Nair, David Boczkowski, Eli Gilboa

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune response, achieved by using a lysosomal targeting sequence to redirect the translated FAP product into the class II presentation pathway, or by covaccination against FAP and a tumor cell-expressed antigen, tyrosinase-related protein 2. No morbidity or mortality was associated with anti-FAP vaccination except for a small delay in wound healing. The study suggests that FAP, a product which is preferentially expressed in tumor-associated fibroblasts, could function as a tumor rejection antigen in a broad range of cancers.

Original languageEnglish
Pages (from-to)11156-11163
Number of pages8
JournalCancer Research
Volume65
Issue number23
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

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Immunotherapy
Fibroblasts
Neoplasms
Proteins
Antigens
Vaccination
Cancer-Associated Fibroblasts
Neoplasm Antigens
Wound Healing
Dendritic Cells
Immunity
Melanoma
Lymphoma
Pathology
Neoplasm Metastasis
Morbidity
Carcinoma
T-Lymphocytes
Lung
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. / Lee, Jaewoo; Fassnacht, Martin; Nair, Smita; Boczkowski, David; Gilboa, Eli.

In: Cancer Research, Vol. 65, No. 23, 01.12.2005, p. 11156-11163.

Research output: Contribution to journalArticle

Lee, Jaewoo ; Fassnacht, Martin ; Nair, Smita ; Boczkowski, David ; Gilboa, Eli. / Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. In: Cancer Research. 2005 ; Vol. 65, No. 23. pp. 11156-11163.
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