title: Immunomodulatory and Antitumor Effects of a Novel TLR7 Agonist Combined with Lapatinib.
abstract: As new treatment approaches, both immunotherapy and targeted treatments have been used in the clinical treatment of cancers. These therapies are different from traditional surgery, chemotherapy and radiotherapy. Use of a combination of immunotherapy and targeted treatments may improve tumor clearance. We investigated the feasibility of combining tyrosine kinase inhibitors (TKIs, targeted drugs) and SZU-101 (a novel TLR7 agonist synthesized by our laboratory). Thirteen different TKIs were combined with or without SZU-101 and studied to determine their effects on immunocytes. On the basis of the distinctive results, lapatinib and sunitinib were selected for further tumor-inhibition investigation and determination of the underlying mechanism. Interestingly, we found lapatinib to work better with SZU-101, enhancing tumor clearance in vivo, without affecting the TLR7-NF-κB pathway activated by the TLR7 agonist in mouse spleen lymphocytes and bone marrow dendritic cells (BMDCs).
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Jin
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Conjugenix company of Shenzhen, Shenzhen 518063, People's Republic of China.
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
authors.affiliation: National-Regional Key Technology Engineering Laboratory for Synthetic Biology of Medicine, Shenzhen University, Shenzhen 518060, People's Republic of China.|Cancer Research Center, Shenzhen University, Shenzhen 518060, People's Republic of China.|Department of Pharmacy, School of Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, People's Republic of China.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D007167:Immunotherapy; D007211:Indoles / Q000494:pharmacology; D000077341:Lapatinib; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology; D000077210:Sunitinib; D051199:Toll-Like Receptor 7 / Q000819:agonists*
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D008562:Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011799:Quinazolines; C000604281:SZU-101; D013386:Succinates; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D000077341:Lapatinib; D011505:Protein-Tyrosine Kinases; D000225:Adenine; D000077210:Sunitinib