Evidence map›Paper›PMID 35708974›Full record

ArticlemAbs

Development of disulfide-stabilized Fabs for targeting of antibody-directed nanotherapeutics.

Melissa L Geddie, Dmitri B Kirpotin, Neeraj Kohli, Tad Kornaga, Bjoern Boll, Maja Razlog, Daryl C Drummond, Alexey A Lugovskoy

Abstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Reprogramming CD22 CAR-T cells in vivo using CD8-targeted mRNA-LNPs to treat hematological malignancies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Review
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

8 authors.

Melissa L GeddieDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Dmitri B KirpotinDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Neeraj KohliDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Tad KornagaDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Bjoern BollDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Maja RazlogDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Daryl C DrummondDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.
Alexey A LugovskoyDiscovery, Merrimack Pharmaceuticals, Inc, Cambridge, Massachusetts, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-directed nanotherapeutics (ADNs) represent a promising delivery platform for selective delivery of an encapsulated drug payload to the site of disease that improves the therapeutic index. Although both single-chain Fv (scFv) and Fab antibody fragments have been used for targeting, no platform approach applicable to any target has emerged. scFv can suffer from intrinsic instability, and the Fabs are challenging to use due to native disulfide over-reduction and resulting impurities at the end of the conjugation process. This occurs because of the close proximity of the disulfide bond connecting the heavy and light chain to the free cysteine at the C-terminus, which is commonly used as the conjugation site. Here we show that by engineering an alternative heavy chain-light chain disulfide within the Fab, we can maintain efficient conjugation while eliminating the process impurities and retaining stability. We have demonstrated the utility of this technology for efficient ADN delivery and internalization for a series of targets, including EphA2, EGFR, and ErbB2. We expect that this technology will be broadly applicable for targeting of nanoparticle encapsulated payloads, including DNA, mRNA, and small molecules.

Indexed as

NanoparticlesSingle-Chain AntibodiesDisulfidesImmunoglobulin Fab FragmentsDisulfidesImmunoglobulin Fab FragmentsSingle-Chain Antibodiesantibody-drug conjugateantibody engineeringAntibody fragmentdevelopabilityliposomemanufacturabilitystability

Identifiers

PMID35708974
PMCPMC9225506

What OpenQuestion holds

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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.