{"doi":"10.1101/2021.11.18.469110","title":"Eliminating fibroblast activation protein-α expressing cells by photoimmunotheranostics","abstract":"Abstract Photoimmunotherapy (PIT) using an antibody conjugated to a near infrared dye IR700 is achieving significant success in target-specific elimination of cells. Fibroblast activation protein alpha (FAP-α) is an important target in cancer because of its expression by cancer associated fibroblasts (CAFs) as well as by some cancer cells. CAFs that express FAP-α have protumorigenic and immune suppressive functions. Using immunohistochemistry of human breast cancer tissue microarrays, we identified an increase of FAP-α+ CAFs in invasive breast cancer tissue compared to adjacent normal tissue. We found FAP-α expression increased in fibroblasts co-cultured with cancer cells. In proof-of-principle studies, we engineered human FAP-α overexpressing MDA-MB-231 and HT-1080 cancer cells and murine FAP-α overexpressing NIH-3T3 fibroblasts to evaluate several anti-FAP-α antibodies and selected AF3715 based on its high binding-affinity with both human and mouse FAP-α. After conjugation of AF3715 with the phthalocyanine dye IR700, the resultant antibody conjugate, FAP-α-IR700, was evaluated in cells and tumors for its specificity and effectiveness in eliminating FAP-α expressing cell populations with PIT. FAP-α-IR700-PIT resulted in effective FAP-α-specific cell killing in the engineered cancer cells and in two patient-derived CAFs in a dose-dependent manner. Following an intravenous injection, FAP-α-IR700 retention was three-fold higher than IgG-IR700 in FAP-α overexpressing tumors, and two-fold higher compared to wild-type tumors. FAP-α-IR700-PIT resulted in significant growth inhibition of tumors derived from FAP-α overexpressing human cancer cells. A reduction of endogenous FAP-α+ murine CAFs was identified at 7 days after FAP-α-IR700-PIT. FAP-α-targeted NIR-PIT presents a promising strategy to eliminate FAP-α+ CAFs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":222082,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257970,"name":"James D. Barnett","orcid":"0000-0002-4692-6656","position":1,"is_corresponding":false},{"id":299501,"name":"Balaji Krishnamachary","orcid":"0000-0001-6137-5832","position":2,"is_corresponding":false},{"id":365354,"name":"Yelena Mironchik","orcid":null,"position":3,"is_corresponding":false},{"id":254692,"name":"Catherine K. Luo","orcid":"0000-0002-2646-9566","position":4,"is_corresponding":false},{"id":262824,"name":"Hisataka Kobayashi","orcid":"0000-0003-1019-4112","position":5,"is_corresponding":false},{"id":272184,"name":"Zaver M. Bhujwalla","orcid":"0000-0002-6617-9360","position":6,"is_corresponding":false},{"id":272183,"name":"Jiefu Jin","orcid":"0000-0002-5318-1111","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}