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Record W4407409544 · doi:10.1080/08820139.2025.2462536

Variable Lymphocyte Receptor B Technologies – Are They Ready for Prime Time?

2025· review· en· W4407409544 on OpenAlex
Arundhati G. Nair, Götz R. A. Ehrhardt, Eyal Grunebaum

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueImmunological Investigations · 2025
Typereview
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersSick Kids Foundation
KeywordsReceptorCommon variable immunodeficiencyLymphocytePrime (order theory)ImmunologyBiologyComputational biologyGeneticsChemistryAntibodyMathematicsCombinatorics

Abstract

fetched live from OpenAlex

Variable Lymphocyte Receptors (VLRs) are the molecules used by jawless vertebrates, lampreys and hagfish, to recognize antigens, akin to the antibodies (Abs) of jawed vertebrates. The unique architecture and evolutionary distance of VLRB Abs enable their binding to epitopes not readily recognized by conventional mammalian Abs. The single gene-polypeptide nature of the secreted VLRB Abs allows for efficient genetic editing and production of VLRB monoclonal Abs (mAbs), which are stable in diverse environments. VLRB Abs can also be modified into scaffolds, known as Repebodies, for efficient protein targeting.Objective To review the current and the potential research and clinical use of VLRBs.Methods A literature search was conducted for English studies published in the past 20 years using the terms “Variable Lymphocyte Receptor,” “VLR,” “VLRB” or “Repebody.” Only primary reports were included.Results VLRB-based technologies are currently being investigated for diagnosis, imaging, and treatment of diverse conditions including solid organ and hematological malignancies, infectious diseases, autoimmunity, and degenerative and metabolic disorders. VLRB mAbs can be used to directly recognize disease biomarkers, such as B cells from chronic lymphocytic leukemia, or to deliver drugs to the brain or cancer cells. The VLRB C-terminal multimerization domain has been utilized to create vaccines while VLR-based chimeric antigen receptor (CAR) T cell constructs are being investigated for cancer therapies.Conclusions The extensive knowledge gained with VLRB mAbs in diverse in vitro and in vivo models emphasizes their promise for translation into clinical applications and readiness for prime time.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.974
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.123
GPT teacher head0.385
Teacher spread0.262 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it