Welcome to the Recombinant Antibody Network

@article{pmid42873839,

title = {ACKR3 Establishes a Squamous-Restricted Immune Checkpoint Axis in Lung Squamous Cell Carcinoma},

author = {Angeliki Karatza and Kaan Kumru and Jaylen M Powell and Chengwei Peng and Yuan Hao and Metamia Ciampricotti and Dimitris Nasias and Hai Hu and Muhammad Elnaggar and Maayan Pour and Alison Chafitz and Yeuan Ting Lee and Priyanka Sahu and Yi Jer Tan and Yun Xue and Ruveyda Ayasun and Alfonso Lopez and Magdalena A Ploszaj and Daniel Andrussier and Yun Zhang and Fiona Sherman and Cynthia A Loomis and Peter Meyn and Jonathan So and Salman R Punekar and Rajwanth Veluswamy and James A Wells and Dafna Bar-Sagi and Kwok-Kin Wong},

doi = {10.1158/0008-5472.CAN-25-5347},

issn = {1538-7445},

year  = {2026},

date = {2026-10-01},

urldate = {2026-10-01},

journal = {Cancer Res},

abstract = {Lung squamous cell carcinoma (LUSC) is an aggressive subtype of non-small cell lung cancer with limited targeted therapeutic options and incompletely defined immune-regulatory dependencies. Here, we identified atypical chemokine receptor 3 (ACKR3) as a squamous-enriched regulator that restrains malignant progression in LUSC. Integrative analyses of human LUSC datasets, autochthonous genetically engineered mouse models, and ex vivo organoid systems showed that ACKR3 loss accelerated tumor growth and remodeled the immune microenvironment, marked by reduced CD8⁺ T cell infiltration and increased T cell exhaustion. Mechanistically, ACKR3 limited activation of the MIF-CD74-PD-L1 axis, thereby constraining tumor-cell PD-L1 expression and preserving antitumor immune surveillance. In preclinical LUSC models, treatment with the ACKR3-directed PD-L1 degrader KineTAC, a bispecific molecule that co-engages ACKR3 and PD-L1 to promote lysosomal degradation of PD-L1, enhanced antitumor efficacy, particularly in combination with chemotherapy. Together, these findings define ACKR3 as a squamous-associated immune checkpoint regulator and nominate ACKR3-directed PD-L1 degradation as a tumor-selective therapeutic strategy for LUSC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42757708,

title = {Strategy for modular assembly of tetravalent, multispecific antibodies},

author = {Evan Mallette and Levi L Blazer and Craig A Hokanson and Chao Chen and Julia Garcia Perez and Alevtina Pavlenco and Lynda Ploder and Alexander U Singer and Michael D L Suits and Sunil Bhakta and Jagath R Junutula and Jarrett J Adams and Sachdev S Sidhu},

doi = {10.1002/pro.70797},

issn = {1469-896X},

year  = {2026},

date = {2026-10-01},

urldate = {2026-10-01},

journal = {Protein Sci},

volume = {35},

number = {10},

pages = {e70797},

abstract = {Multispecific, multivalent antibodies (Abs) are a burgeoning class of drugs that dramatically expand the pharmacological repertoire beyond traditional therapeutic Abs. Here, we present a simple, modular approach to developing multispecific, multivalent Abs based on a Fab-phage library with a single light chain. Using this library, we created three Abs targeting unique sites on programmed death-ligand 1 (PD-L1) and another antibody targeting CD30. Biophysical and cellular characterization of these Abs demonstrated their functional equivalence to clinically relevant Abs targeting PD-L1 or CD30. We then combined these paratopes into a series of bispecific, tetravalent, triparatopic Abs that retained the functionality of the parental Abs. Structural analysis of each of the Abs in complex with their cognate antigens demonstrated the adaptability of the common light chain to form diverse paratopes with an array of distinct heavy chains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41807832,

title = {Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core},

author = {J Andrew N Alexander and Shu-Yu Chen and Somnath Mukherjee and Mario de Capitani and Rossitza N Irobalieva and Lorenzo Rossi and Parth Agrawal and Julia Kowal and Matheus A Meirelles and Markus Aebi and Jean-Louis Reymond and Anthony A Kossiakoff and Sereina Riniker and Kaspar P Locher},

doi = {10.1038/s41589-026-02164-7},

issn = {1552-4469},

year  = {2026},

date = {2026-09-01},

urldate = {2026-09-01},

journal = {Nat Chem Biol},

volume = {22},

number = {9},

pages = {1501--1513},

abstract = {Asparagine-linked glycans are essential for the maturation and function of most eukaryotic secretory proteins. The biosynthesis and transfer of dolichylpyrophosphate-anchored GlcNAcManGlc glycan is a highly conserved process occurring in the endoplasmic reticulum (ER) membrane and involving over a dozen membrane proteins whose dysfunction is linked to congenital disorders of glycosylation (CDGs). Three membrane-integral mannosyltransferases, ALG3, ALG9 and ALG12, mediate four consecutive mannosylation reactions that convert GlcNAcMan to GlcNAcMan. Here, using chemoenzymatically synthesized lipid-linked glycan donor and acceptor analogs, we recapitulated this biosynthetic pathway in vitro. High-resolution cryo-electron microscopy structures of pseudo-Michaelis complexes of each step revealed how the branched glycan is accurately synthesized and unwanted side products are averted. Molecular dynamics simulations and mutagenesis studies uncovered a subtle but precise mechanism selecting the dolichylphosphomannose donor substrate over dolichylphosphoglucose, which is also present in the ER membrane. Our results also provide mechanistic explanations for enzyme dysfunction in CDGs and offer opportunities for N-glycan engineering.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}