A tumor-targeted immune checkpoint blocker. 2019

Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China.

To direct checkpoint inhibition to the tumor microenvironment, while avoiding systemic immune activation, we have synthesized a bispecific antibody [norleucine4, d-Phe7]-melanocyte stimulating hormone (NDP-MSH)-antiprogrammed cell death-ligand 1 antibody (αPD-L1) by conjugating a melanocyte stimulating hormone (α-MSH) analog to the antiprogrammed cell death-ligand 1 to (αPD-L1) antibody avelumab. This bispecific antibody can bind to both the melanocortin-1 receptor (MC1R) and to PD-L1 expressed on melanoma cells and shows enhanced specific antitumor efficacy in a syngeneic B16-SIY melanoma mouse model compared with the parental antibody at a 5 mg/kg dose. Moreover, the bispecific antibody showed increased infiltrated T cells in the tumor microenvironment. These results suggest that a tumor-targeted PD-L1-blocking bispecific antibody could have a therapeutic advantage in vivo, especially when used in combination with other checkpoint inhibitors.

UI MeSH Term Description Entries
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D008546 Melanoma, Experimental Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA. B16 Melanoma,Melanoma, B16,Melanoma, Cloudman S91,Melanoma, Harding-Passey,Experimental Melanoma,Experimental Melanomas,Harding Passey Melanoma,Melanomas, Experimental,B16 Melanomas,Cloudman S91 Melanoma,Harding-Passey Melanoma,Melanoma, Harding Passey,Melanomas, B16,S91 Melanoma, Cloudman
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000521 alpha-MSH A 13-amino acid peptide derived from proteolytic cleavage of ADRENOCORTICOTROPIC HORMONE, the N-terminal segment of ACTH. ACTH (1-13) is amidated at the C-terminal to form ACTH (1-13)NH2 which in turn is acetylated to form alpha-MSH in the secretory granules. Alpha-MSH stimulates the synthesis and distribution of MELANIN in MELANOCYTES in mammals and MELANOPHORES in lower vertebrates. MSH, alpha,alpha Intermedin,alpha-Melanocyte-Stimulating Hormone,(Des-Acetyl)-alpha-MSH,(Desacetyl)alpha-MSH,ACTH (1-13),ACTH (1-13)NH2,ACTH(1-13),Acetylated ACTH (1-13)NH2,Adrenocorticotropin (1-13)NH2,DE-alpha-MSH,Des-Acetyl MSH,Desacetyl alpha-MSH,Desacetyl alpha-Melanocyte-Stimulating Hormone,MSH, (Desacetyl)alpha-,alpha-Melanotropin,Desacetyl alpha MSH,Desacetyl alpha Melanocyte Stimulating Hormone,Hormone, Desacetyl alpha-Melanocyte-Stimulating,Hormone, alpha-Melanocyte-Stimulating,Intermedin, alpha,MSH, Des-Acetyl,alpha MSH,alpha Melanocyte Stimulating Hormone,alpha Melanotropin,alpha-MSH, Desacetyl,alpha-Melanocyte-Stimulating Hormone, Desacetyl
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057809 HEK293 Cells A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5. 293T Cells,HEK 293 Cell Line,HEK 293 Cells,Human Embryonic Kidney Cell Line 293,Human Kidney Cell Line 293,293 Cell, HEK,293 Cells, HEK,293T Cell,Cell, 293T,Cell, HEK 293,Cell, HEK293,Cells, 293T,Cells, HEK 293,Cells, HEK293,HEK 293 Cell,HEK293 Cell

Related Publications

Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
July 2023, Journal of controlled release : official journal of the Controlled Release Society,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
January 2016, Postepy higieny i medycyny doswiadczalnej (Online),
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
January 2020, Frontiers in cell and developmental biology,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
January 2019, The AAPS journal,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
November 2021, Emerging topics in life sciences,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
December 2021, Journal of controlled release : official journal of the Controlled Release Society,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
January 2017, Oncoimmunology,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
July 2021, ACS applied materials & interfaces,
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
September 2020, European journal of cancer (Oxford, England : 1990),
Yuhan Zhang, and Changming Fang, and Rongsheng E Wang, and Ying Wang, and Hui Guo, and Chao Guo, and Lijun Zhao, and Shuhong Li, and Xia Li, and Peter G Schultz, and Yu J Cao, and Feng Wang
January 2016, Cancer journal (Sudbury, Mass.),
Copied contents to your clipboard!