Delving into the Latest Updates on CD47–LLO with Synapse

Overview

Basic Info

Drug Type

Antibody toxin conjugate

Synonyms-

Target

CD47

Action

inhibitors

Mechanism

CD47 inhibitors(Cluster of differentiation 47 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

University of Texas Health Science Center At San Antonio

Active Organization

University of Texas Health Science Center At San Antonio

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

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Author: Antony, Abin ; Grippin, Adam J ; Koong, Albert C ; Schrank, Benjamin R ; Chang, Mengyu ; Li, Jing ; Kim, Betty Y S ; Gallup, Thomas D ; Tran, Nhat ; Wang, Yifan ; Yun, Kyuson ; Wu, Annette ; Ma, Yifan ; Jeong, Seong Dong ; Lee, DaeYong ; Huntoon, Kristin ; Dong, Shiyan ; Jiang, Wen ; Ha, JongHoon ; Edwards, Jared ; Kang, Minjeong

Antigen-presenting cells phagocytose tumor cells and subsequently cross-present tumor-derived antigens. However, these processes are impeded by phagocytosis checkpoints and inefficient cytosolic transport of antigenic peptides from phagolysosomes. Here, using a microbial-inspired strategy, we engineered an antibody-toxin conjugate (ATC) that targets the 'don't eat me' signal CD47 linked to the bacterial toxin listeriolysin O from the intracellular bacterium Listeria monocytogenes via a cleavable linker (CD47-LLO). CD47-LLO promotes cancer cell phagocytosis by macrophages followed by LLO release and activation to form pores on phagolysosomal membranes that enhance antigen cross-presentation of tumor-derived peptides and activate cytosolic immune sensors. CD47-LLO treatment in vivo significantly inhibited the growth of both localized and metastatic breast and melanoma tumors and improved animal survival as a monotherapy or in combination with checkpoint blockade. Together, these results demonstrate that designing ATCs to promote immune recognition of tumor cells represents a promising therapeutic strategy for treating multiple cancers.

100 Deals associated with CD47–LLO

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	United States	University of Texas Health Science Center At San Antonio	25 Feb 2025

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Clinical Result

Indication

Phase

Evaluation

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Translational Medicine

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Deal

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Core Patent

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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