Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro

Teichgräber, Volker; Monasterio, Carmen; Chaitanya, Krishna; Boger, Regina; Gordon, Katrin; Dieterle, Thomas; Jäger, Dirk; Bauer, Stefan

doi:10.1016/j.advms.2015.04.006

Cited by 72 publications

(52 citation statements)

References 39 publications

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“…Furthermore, CAFs express fibroblast activation protein (FAP), a type II transmembrane protein that is overexpressed in over 90% of CAFs associated with colon, breast, and lung carcinomas [132]. Poor intratumoral uptake of chemotherapeutic agents has been associated with expression and organization of collagen type 1, which is mainly produced by FAP [133], and treatment with anti-FAP antibodies or siRNA against FAP has shown to suppress pro-tumorigenic activity [134]. An oral DNA vaccine targeting FAP suppressed primary tumor cell growth and metastasis, decreased collagen type I expression, and increased drug uptake by 70% [135].…”

Section: Targeting Constituents Within the Tumor Microenvironmentmentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

437

258

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a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

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Section: Targeting Constituents Within the Tumor Microenvironmentmentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

437

258

View full text Add to dashboard Cite

show abstract

“…In this context, it is conceivable that surface markers expressed mainly, if not exclusively, by MSC should be considered to regulate the TME. Indeed, FAP, CD73, and CD105 can be considered as suitable markers to target MSC [11,13,14,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150]. In hematological malignancies, but also in solid tumors, the administration of immunomodulatory drugs (IMiDs) derived from their prototype Thalidomide to CC-122 has given very attractive results because these compounds can hit MSC besides tumor cells [151,152,153].…”

Section: Drugs That Can Influence Msc-mediated Immune Regulationmentioning

confidence: 99%

“…Several kinds, compositions, and modes of administration of anti-tumor vaccines have been used with different results [160,161,162,163,164,165,166,167]. More recently, the focus of anti-tumor vaccines has been moved from tumor cells to TME too [7,9,10,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175]. Indeed, the possibility of targeting tumor endothelial cells or the VEGF signaling axis with specific vaccines has been assessed in preclinical studies, and clinical trials are ongoing [168].…”

Section: Msc As Target Cells For Anti-tumor Vaccinesmentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

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The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

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“…Targeting FAP α genetically with vaccines, with antibodies, or with pharmacological agents, impairs tumor progression in several preclinical cancer models [59-61]. Therefore, FAP α is considered to be an adaptive tumor-associated antigen for tumor immunotherapy.…”

Section: The Fap α-Targeted Immunotherapy Strategymentioning

confidence: 99%

The application of the fibroblast activation protein α-targeted immunotherapy strategy

Jiang

et al. 2016

Oncotarget

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Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target.

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Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro

Cited by 72 publications

References 39 publications

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

The application of the fibroblast activation protein α-targeted immunotherapy strategy

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