Search: onr:"swepub:oai:lup.lub.lu.se:2cfc42a5-f203-4a41-bbde-203e6e47e467" >
The Bispecific Tumo...
The Bispecific Tumor Antigen-Conditional 4-1BB x 5T4 Agonist, ALG.APV-527, Mediates Strong T-Cell Activation and Potent Antitumor Activity in Preclinical Studies
-
- Nelson, Michelle H. (author)
- Aptevo Therapeutics
-
- Fritzell, Sara (author)
- Alligator Biosciences AB
-
- Miller, Robert (author)
- Aptevo Therapeutics
-
show more...
-
- Werchau, Doreen (author)
- Alligator Biosciences AB
-
- Van Citters, Danielle (author)
- Aptevo Therapeutics
-
- Nilsson, Anneli (author)
- Alligator Biosciences AB
-
- Misher, Lynda (author)
- Aptevo Therapeutics
-
- Ljung, Lill (author)
- Alligator Biosciences AB
-
- Bader, Robert (author)
- Aptevo Therapeutics
-
- Deronic, Adnan (author)
- Alligator Biosciences AB
-
- Chunyk, Allison G. (author)
- Aptevo Therapeutics
-
- Schultz, Lena (author)
- Alligator Biosciences AB
-
- Varas, Laura A. (author)
- Alligator Biosciences AB
-
- Rose, Nadia (author)
- SARomics Biostructures AB
-
- Håkansson, Maria (author)
- SARomics Biostructures AB
-
- Gross, Jane (author)
- Aptevo Therapeutics
-
- Furebring, Christina (author)
- Alligator Biosciences AB
-
Pavlik, Peter (author)
-
- Sundstedt, Anette (author)
- Alligator Biosciences AB
-
Veitonmäki, Niina (author)
-
Ramos, Hilario J. (author)
-
- Säll, Anna (author)
- Alligator Biosciences AB
-
Dahlman, Anna (author)
-
Bienvenue, David (author)
-
- von Schantz, Laura (author)
- Alligator Biosciences AB
-
McMahan, Catherine J. (author)
-
- Askmyr, Maria (author)
- Alligator Biosciences AB
-
Hernandez-Hoyos, Gabriela (author)
-
- Ellmark, Peter (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Alligator Biosciences AB
-
show less...
-
(creator_code:org_t)
- 2023
- 2023
- English 13 s.
-
In: Molecular Cancer Therapeutics. - 1538-8514. ; 22:1, s. 89-101
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 4-1BB (CD137) is an activation-induced costimulatory receptor that regulates immune responses of activated CD8 T and natural killer cells, by enhancing proliferation, survival, cytolytic activity, and IFNγ production. The ability to induce potent antitumor activity by stimulating 4-1BB on tumor-specific cytotoxic T cells makes 4-1BB an attractive target for designing novel immuno-oncology therapeutics. To minimize systemic immune toxicities and enhance activity at the tumor site, we have developed a novel bispecific antibody that stimulates 4-1BB function when co-engaged with the tumor-associated antigen 5T4. ALG.APV-527 was built on the basis of the ADAPTIR bispecific platform with optimized binding domains to 4-1BB and 5T4 originating from the ALLIGATOR-GOLD human single-chain variable fragment library. The epitope of ALG.APV-527 was determined to be located at domain 1 and 2 on 4-1BB using X-ray crystallography. As shown in reporter and primary cell assays in vitro, ALG.APV-527 triggers dose-dependent 4-1BB activity mediated only by 5T4 crosslinking. In vivo, ALG.APV-527 demonstrates robust antitumor responses, by inhibiting growth of established tumors expressing human 5T4 followed by a long-lasting memory immune response. ALG.APV-527 has an antibody-like half-life in cynomolgus macaques and was well tolerated at 50.5 mg/kg. ALG.APV-527 is uniquely designed for 5T4-conditional 4-1BB-mediated antitumor activity with potential to minimize systemic immune activation and hepatotoxicity while providing efficacious tumor-specific responses in a range of 5T4-expressing tumor indications as shown by robust activity in preclinical in vitro and in vivo models. On the basis of the combined preclinical dataset, ALG.APV-527 has potential as a promising anticancer therapeutic for the treatment of 5T4-expressing tumors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
-
Nelson, Michelle ...
-
Fritzell, Sara
-
Miller, Robert
-
Werchau, Doreen
-
Van Citters, Dan ...
-
Nilsson, Anneli
-
show more...
-
Misher, Lynda
-
Ljung, Lill
-
Bader, Robert
-
Deronic, Adnan
-
Chunyk, Allison ...
-
Schultz, Lena
-
Varas, Laura A.
-
Rose, Nadia
-
Håkansson, Maria
-
Gross, Jane
-
Furebring, Chris ...
-
Pavlik, Peter
-
Sundstedt, Anett ...
-
Veitonmäki, Niin ...
-
Ramos, Hilario J ...
-
Säll, Anna
-
Dahlman, Anna
-
Bienvenue, David
-
von Schantz, Lau ...
-
McMahan, Catheri ...
-
Askmyr, Maria
-
Hernandez-Hoyos, ...
-
Ellmark, Peter
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Molecular Cancer ...
- By the university
-
Lund University