Fibroblast Activation Protein (FAP)-Targeted Antifibrotic Therapy

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Abstract

Researchers at Purdue University have developed new drugs to image and therapeutically target fibroblast activation protein (FAP) in solid tumors. The drugs are composed of a FAP-alpha-targeting moiety, a linker, and an inhibitory agent. The inhibitory agent inhibits a pathway associated with the formation of cancer-associated fibroblasts (CAFs), cells that regulate tumor growth. CAFs express FAP-alpha, a protein that affects the tumor microenvironment. Along with reducing CAF formation, the inhibitory agent also reduces collagen I formation, a protein that is associated with tumor growth. The researchers’ drugs quickly clear from tissues not expressing FAP-alpha. The Purdue-developed targeted therapy may be used to target over 50 types of cancer. It also has the potential to treat fibrotic diseases or disorders such as pulmonary fibrosis.

Related Publications:

Roy J, Hettiarachchi SU, Kaake M, Mukkamala R, Low PS. Design and validation of fibroblast activation protein alpha targeted imaging and therapeutic agents. Theranostics. doi: 10.7150/thno.41409.

Hettiarachchi SU, Li Y, Roy J, Zhang F, Puchulu-Campanella E, Lindeman SD, Srinivasarao M, Tsoyi K, Liang X, Ayaub EA, Nickerson-Nutter C, Rosas IO, Low PS. Targeted inhibition of PI3 kinase/mTOR specifically in fibrotic lung fibroblasts suppresses pulmonary fibrosis in experimental models. Science Translational Medicine. doi: 10.1126/scitranslmed.aay3724.

Technology Validation: FAP-targeted optical or radio imaging was performed to determine the specificity and selectivity of the FAP-targeting drugs for FAP in vitro and in vivo. The Purdue-developed FAP-targeting drugs showed high binding specificity and affinity in the low nanomolar range. Injection of the FAP-targeting drugs into tumor-bearing mice enabled detection of tumor xenografts with little off-target uptake. Systemic administration of the drug also promoted eradication of solid tumors with no evidence of gross toxicity to the animals.

Advantages: – Targets CAFs and FAP-alpha – May treat over 50 types of solid cancers – Can be formulated as liquid suspension or solid granules

Applications: – Targeted therapy for cancer in humans or animals – Treatment of fibrotic diseases

Advantages

Targets CAFs and FAP-alpha

May treat over 50 types of solid cancer

Can be formulated as liquid suspension or solid granules

Potential Applications

Targeted therapy for cancer in humans and animals

Treatment of Fibrotic diseases

Contact Information

Name: Brooke L Beier

Email: blbeier@prf.org

Phone: 810-571-2387