Evidence map›Paper›PMID 34169228›Full record

ArticleAntibody therapeutics2021

An optimal antitumor response by a novel CEA/CD3 bispecific antibody for colorectal cancers.

Ninghai Wang, Harshal Patel, Irene C Schneider, Xin Kai, Avanish K Varshney, Li Zhou

Open access · goldAbstract read
In one paragraph

Article in Antibody therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% of its field
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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Ninghai WangAntibody and Cell Therapy Group, Boan Boston LLC, Woburn, MA 01801, USA.
Harshal PatelAntibody and Cell Therapy Group, Boan Boston LLC, Woburn, MA 01801, USA.
Irene C SchneiderIndependent Consultant, Hanau 63456, Germany.ORCID 0000-0001-5887-4577
Xin KaiAntibody and Cell Therapy Group, Boan Boston LLC, Woburn, MA 01801, USA.
Avanish K VarshneyAntibody and Cell Therapy Group, Boan Boston LLC, Woburn, MA 01801, USA.
Li ZhouAntibody and Cell Therapy Group, Boan Boston LLC, Woburn, MA 01801, USA.
Klinikum Hanau · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCD3-based bispecific T cell engagers (bsTCEs) are one of the most promising bispecific antibodies for effective cancer treatments. To elicit target-specific T cell-mediated cytotoxicity, these bsTCEs contain at least one binding unit directed against a tumor antigen and another binding unit targeting CD3 in T cell receptor complex. Development of CD3-based bsTCEs, however, has been severely hampered by dose-limiting toxicities due to cytokine release syndrome. To address this limitation, we developed a novel functionally trivalent T cell engager (t-TCE) antibody containing affinity-reduced CD3 binding unit positioned to ensure monovalent CD3 engagement, in combination with bivalent tumor antigen binding of carcinoembryonic antigen (CEA).

methodsWe modeled the variable region of anti-CD3 in the complementarity-determining regions of the heavy chain and obtained CD3 binders with reduced binding affinity. Two optimized versions CEA/CD3-v1 and CEA/CD3-v2 were identified and generated in tetravalent format, characterized and compared

resultsOur lead candidate, CEA/CD3-v2, demonstrated subnanomolar binding and picomolar potency against a panel of CEA-expressing cancer cell lines. In addition, we detected reduced T cell cytokine release with potent cytotoxic activity. Our t-TCE CEA/CD3-v2 molecule demonstrated strong antitumor effect in a dose-dependent manner in human peripheral blood mononuclear cell (PBMC) xenograft model. Furthermore, combination of CEA/CD3-v2 with atezolizumab provided synergistic antitumor effect.

conclusionsBecause of its effective tumor cell killing

Indexed as

bispecific antibodycancerCEA/CD3T cell engagertoxicity

Identifiers

PMID34169228
PMCPMC8220303
OpenAlexW3168215742

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.