Previous Article in Journal
Influence and Role of Regulatory B Cells in Organ Transplantation: The State of the Art, Prospects, and Emerging Insights
Previous Article in Special Issue
A Targeted Integration-Based CHO Cell Platform for Simultaneous Antibody Display and Secretion
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibodies
Volume 14
Issue 4
10.3390/antib14040096
antibodies-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB

by
Christina Claus
1,
Claudia Ferrara-Koller
1,
Johannes Sam
1,
Sabine Lang
1,
Rosmarie Albrecht
1,
Regula B. Buser
1,
Esther Bommer
1,
Grégory La Sala
1,
Valeria G. Nicolini
1,*,
Sara Colombetti
2,
Marina Bacac
1,
Pablo Umaña
1 and
Christian Klein
1,3
1
Roche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Wagistrasse 10, 8952 Schlieren, Switzerland
2
Roche Innovation Center Basel, Roche Pharma Research and Early Development (pRED), Grenzacherstrasse 124, 4070 Basel, Switzerland
3
Department of Biochemistry, Faculty of Chemistry and Pharmacy, Ludwig Maximilians University of Munich, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Antibodies 2025, 14(4), 96; https://doi.org/10.3390/antib14040096
Submission received: 27 September 2025 / Revised: 28 October 2025 / Accepted: 5 November 2025 / Published: 7 November 2025
(This article belongs to the Special Issue Emerging Antibody Engineering Strategies and Applications for Immunotherapy of Cancer)
Browse Figure
Versions Notes

Abstract

Background/Objectives: T cell bispecific antibodies (TCBs) result in the activation of T cell receptor signaling upon binding to tumor antigens providing signal 1 to T cells. To enhance and sustain their activity, a co-stimulatory signal 2 is required. Here CEACAM5-targeted 4-1BBL antibody fusion proteins for combination with CEA-TCB (cibisatamab, RG7802) are described in an investigation of the relationship between the CEACAM5 epitope and T cell activity. Methods: CEACAM5-targeted bispecific 4-1BBL antibody fusion proteins (CEA-4-1BBLs) were generated based on different CEACAM5 antibodies and characterized in vitro in Jurkat-4-1BB reporter and PBMC cell assays. The impact of shed CEA on in vitro activity and cynomolgus cross-reactivity was studied. In vivo efficacy was assessed in human stem cell humanized NSG mice xenograft models bearing MKN-45 and HPAFII tumors. Results: MFE23-4-1BBL and Sm9b-4-1BBL showed superior functional activity in Jurkat-4-1BB reporter and primary T cell assays when combined with the CD3 antibody V9, whereas T84.66-LCHA-4-1BBL and A5B7-4-1BBL performed better when combined with CEA-TCB. In humanized NSG mice MKN-45 and HPAFII xenograft models, T84.66-LCHA-4-1BBL mediated the best anti-tumor efficacy. Conclusions: For the assessment of the combination of CEA-TCB with CEA-4-1BBL, co-stimulatory antibody fusion protein in vitro assays are not sufficient to fully capture the complex relationships affecting efficacy. Thus, screening with different cell assays and in vivo efficacy studies in combination with CEA-TCB are essential to select the best candidate. Based on the totality of data on the T84.66-LCHA-4-1BBL antibody fusion protein comprising the CEACAM5 antibody, T84.66-LCHA was selected as the optimal combination partner for CEA-TCB.
Keywords: CEACAM5; 4-1BB; TNFRSF9; CD137; membrane-proximal; membrane-distal; epitope CEACAM5; 4-1BB; TNFRSF9; CD137; membrane-proximal; membrane-distal; epitope
Graphical Abstract

Share and Cite

MDPI and ACS Style

Claus, C.; Ferrara-Koller, C.; Sam, J.; Lang, S.; Albrecht, R.; Buser, R.B.; Bommer, E.; Sala, G.L.; Nicolini, V.G.; Colombetti, S.; et al. CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB. Antibodies 2025, 14, 96. https://doi.org/10.3390/antib14040096

AMA Style

Claus C, Ferrara-Koller C, Sam J, Lang S, Albrecht R, Buser RB, Bommer E, Sala GL, Nicolini VG, Colombetti S, et al. CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB. Antibodies. 2025; 14(4):96. https://doi.org/10.3390/antib14040096

Chicago/Turabian Style

Claus, Christina, Claudia Ferrara-Koller, Johannes Sam, Sabine Lang, Rosmarie Albrecht, Regula B. Buser, Esther Bommer, Grégory La Sala, Valeria G. Nicolini, Sara Colombetti, and et al. 2025. "CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB" Antibodies 14, no. 4: 96. https://doi.org/10.3390/antib14040096

APA Style

Claus, C., Ferrara-Koller, C., Sam, J., Lang, S., Albrecht, R., Buser, R. B., Bommer, E., Sala, G. L., Nicolini, V. G., Colombetti, S., Bacac, M., Umaña, P., & Klein, C. (2025). CEA-4-1BBL: CEACAM5-Targeted 4-1BB Ligand Fusion Proteins for Cis Co-Stimulation with CEA-TCB. Antibodies, 14(4), 96. https://doi.org/10.3390/antib14040096

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop