Evidence map›Paper›PMID 25484041›Full record

ArticlemAbs2015

Comprehensive optimization of a single-chain variable domain antibody fragment as a targeting ligand for a cytotoxic nanoparticle.

Kathy Zhang, Melissa L Geddie, Neeraj Kohli, Tad Kornaga, Dmitri B Kirpotin, Yang Jiao, Rachel Rennard, Daryl C Drummond, Ulrik B Nielsen, Lihui Xu and 1 more

Abstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Application of nanobody‑based CAR‑T in tumor immunotherapy (Review).International journal of molecular medicine · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kathy Zhanga Merrimack Pharmaceuticals, Inc. ; Cambridge , MA USA.
Melissa L Geddie
Neeraj Kohli
Tad Kornaga
Dmitri B Kirpotin
Yang Jiao
Rachel Rennard
Daryl C Drummond
Ulrik B Nielsen
Lihui Xu
Alexey A Lugovskoy

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-targeted nanoparticles have the potential to significantly increase the therapeutic index of cytotoxic anti-cancer therapies by directing them to tumor cells. Using antibodies or their fragments requires careful engineering because multiple parameters, including affinity, internalization rate and stability, all need to be optimized. Here, we present a case study of the iterative engineering of a single chain variable fragment (scFv) for use as a targeting arm of a liposomal cytotoxic nanoparticle. We describe the effect of the orientation of variable domains, the length and composition of the interdomain protein linker that connects VH and VL, and stabilizing mutations in both the framework and complementarity-determining regions (CDRs) on the molecular properties of the scFv. We show that variable domain orientation can alter cross-reactivity to murine antigen while maintaining affinity to the human antigen. We demonstrate that tyrosine residues in the CDRs make diverse contributions to the binding affinity and biophysical properties, and that replacement of non-essential tyrosines can improve the stability and bioactivity of the scFv. Our studies demonstrate that a comprehensive engineering strategy may be required to identify a scFv with optimal characteristics for nanoparticle targeting.

Indexed as

CytotoxinsSingle-Chain AntibodiesAmino Acid SubstitutionAnimalsAntibodies, NeoplasmCell Line, TumorDrug Delivery SystemsHumansMiceNanoparticlesNeoplasmsRecombinant ProteinsAntibodies, NeoplasmCytotoxinsRecombinant ProteinsSingle-Chain Antibodiesantibody-drug conjugateantibody fragmentCDR, complementarity-determining regionCLIA, chelated ligand-induced internalization assayDSF, differential scanning fluorimetryEphA2, ephrin type-A receptor 2FACS, fluorescence-activated cell sortingHTP, high throughputliposomemanufacturabilitynanoparticlescFv, single chain variable fragmentstabilityyeast display

Identifiers

PMID25484041
PMCPMC4622481

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.