Welcome to the Recombinant Antibody Network

@article{pmid40614208,

title = {A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy},

author = {Ainhoa Arina and Edwin Arauz and Elham Masoumi and Karolina W Warzecha and Annika Sääf and Łukasz Widło and Tomasz Slezak and Aleksandra Zieminska and Karolina Dudek and Zachary P Schaefer and Maria Lecka and Svitlana Usatyuk and Ralph R Weichselbaum and Anthony A Kossiakoff},

doi = {10.1126/sciadv.adv4937},

issn = {2375-2548},

year  = {2025},

date = {2025-07-01},

urldate = {2025-07-01},

journal = {Sci Adv},

volume = {11},

number = {27},

pages = {eadv4937},

abstract = {Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR-fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8 T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile "plug-and-play" CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40661577,

title = {Low-density lipoprotein receptor-targeting chimeras for membrane protein degradation and enhanced drug delivery},

author = {Fangzhu Zhao and Yan Wu and Kaitlin Schaefer and Yun Zhang and Kun Miao and Zi Yao and Snehal D Ganjave and Kaan Kumru and Trenton M Peters-Clarke and Alex Inague and James A Olzmann and Kevin K Leung and James A Wells},

doi = {10.1101/2025.06.06.658366},

issn = {2692-8205},

year  = {2025},

date = {2025-06-01},

urldate = {2025-06-01},

journal = {bioRxiv},

abstract = {Antibody-based therapeutics encompass diverse modalities for targeting tumor cells. Among these, antibody-drug conjugates (ADCs) and extracellular targeted protein degradation (eTPD) specifically depend on efficient lysosomal trafficking for activity. However, many tumor antigens exhibit poor internalization, limiting ADC effectiveness. To address this, we developed low-density lipoprotein receptor-targeting chimeras (LIPTACs), leveraging the constitutive endocytic and recycling activity of the LDLR to enhance lysosomal delivery. LIPTACs enable efficient and selective degradation of diverse extracellular membrane proteins. Additionally, by coupling LIPTACs with cytotoxic payloads to generate degrader-drug conjugates, we can achieve superior intracellular delivery and enhanced cytotoxicity compared to conventional ADCs. The dual modality addresses key challenges of inadequate internalization in conventional ADCs and cytotoxic potency for current eTPD strategies. Our findings demonstrate that LDLR-mediated trafficking can enhance eTPD and ADCs, providing a hybrid blueprint for developing next-generation antibody therapeutics with broader utility and improved efficacy in cancer treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40575703,

title = {Biophysical basis of tight junction barrier modulation by a pan-claudin-binding molecule},

author = {Chinemerem P Ogbu and Mason de Las Alas and Alexandria M Mandriota and Xiangdong Liu and Srajan Kapoor and Jagrity Choudhury and Yasmeen N Ruma and Michael C Goodman and Charles R Sanders and Tamir Gonen and Anthony A Kossiakoff and Michael E Duffey and Alex J Vecchio},

doi = {10.1093/pnasnexus/pgaf189},

issn = {2752-6542},

year  = {2025},

date = {2025-06-01},

urldate = {2025-06-01},

journal = {PNAS Nexus},

volume = {4},

number = {6},

pages = {pgaf189},

abstract = {Claudins are a 27-member family of membrane proteins that form and fortify specialized cell contacts in endothelium and epithelium called tight junctions. Tight junctions restrict paracellular transport through tissues by forming molecular barriers between cells. Claudin-binding molecules thus hold promise for modulating tight junction permeability to deliver drugs or as therapeutics to treat tight junction-linked disease. The development of claudin-binding molecules, however, is hindered by their physicochemical intractability and small targetable surfaces. Here, we determine that a synthetic antibody fragment (sFab) that we developed binds with nanomolar affinity directly to 10 claudin subtypes and other distantly related claudin family members but not to other tight junction-localized membrane proteins. It does so by targeting the extracellular surfaces of claudins, which we verify by applying this sFab to a model intestinal epithelium and observe that it opens paracellular barriers comparable to a known, but application limited, tight junction modulating protein. This pan-claudin-binding molecule holds potential for both basic and translational applications as it is a probe of claudin and tight junction structure in vitro and in vivo and a tool to modulate the permeability of tight junctions broadly across tissue barriers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}