Evidence map›Paper›PMID 33986124›Full record

ArticleJournal for immunotherapy of cancer2021

Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release.

Jeong A Park, Brian H Santich, Hong Xu, Lawrence G Lum, Nai-Kong V Cheung

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.5field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026
    Review
  3. Article
  4. Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.Advances in experimental medicine and biology · 2026
    Review
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  19. Promise and Challenges of T Cell Immunotherapy for Osteosarcoma.International journal of molecular sciences · 2023
    Review
  20. Article
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

5 authors at 2 institutions in 1 country.

Jeong A ParkPediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0003-3690-6747
Brian H SantichPediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Hong XuPediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Lawrence G LumMedicine, University of Virginia, Charlottesville, Virginia, USA.
Nai-Kong V CheungPediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA cheungn@mskcc.org.ORCID 0000-0001-6323-5171
Memorial Sloan Kettering Cancer Center · USUniversity of Virginia · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
Targeting Oncogenic Pathways in Genetically Complex SarcomasP50CA217694 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI William D. Tap · 2018 to 2026
$21.5M
Targeting Neuroblastoma with armed T cellsR01CA182526 · NCI · WAYNE STATE UNIVERSITY · PI CHEUNG, NAI-KONG V, LUM, LAWRENCE G · 2014 to 2019
$3.9M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA044579NCI NIH HHS P50 CA217694NCI NIH HHS R01 CA182526
6 · The paper itself

Abstract

backgroundT cell-based immunotherapies using chimeric antigen receptors (CAR) or bispecific antibodies (BsAb) have produced impressive responses in hematological malignancies. However, major hurdles remained, including cytokine release syndrome, neurotoxicity, on-target off-tumor effects, reliance on autologous T cells, and failure in most solid tumors. BsAb armed T cells offer a safe alternative.

methodsWe generated ex vivo armed T cells (EATs) using IgG-[L]-scFv-platformed BsAb, where the anti-CD3 (huOKT3) scFv was attached to the light chain of a tumor-binding IgG. BsAb density on EAT, in vitro cytotoxicity, cytokine release, in vivo trafficking into tumors, and their antitumor activities were evaluated in multiple cancer cell lines and patient-derived xenograft mouse models. The efficacy of EATs after cryopreservation was studied, and gamma delta (γδ) T cells were investigated as unrelated alternative effector T cells.

resultsThe antitumor potency of BsAb armed T cells was substantially improved using the IgG-[L]-scFv BsAb platform. When compared with separate BsAb and T cell injection, EATs released less TNF-α, and infiltrated tumors faster, while achieving robust antitumor responses. The in vivo potency of EAT therapy depended on BsAb dose for arming, EAT cell number per injection, total number of EAT doses, and treatment schedule intensity. The antitumor efficacy of EATs was preserved following cryopreservation, and EATs using γδ T cells were safe and as effective as αβ T cell-EATs.

conclusionsEATs exerted potent antitumor activities against a broad spectrum of human cancer targets with remarkable safety. The antitumor potency of EATs depended on BsAb dose, cell number and total dose, and schedule. EATs were equally effective after cryopreservation, and the feasibility of third-party γδ-EATs offered an alternative for autologous T cell sources.

Indexed as

Immunotherapy, AdoptiveLymphocyte ActivationAnimalsAntibodies, BispecificCell Line, TumorCell MovementCoculture TechniquesCytokinesCytotoxicity, ImmunologicHumansIntraepithelial LymphocytesLymphocytes, Tumor-InfiltratingMaleMiceMice, Inbred BALB CMice, KnockoutAntibodies, BispecificCytokinesadoptiveimmunotherapyinvestigationalneuroblastomasarcomatherapiestranslational medical research

Identifiers

PMID33986124
PMCPMC8126293
OpenAlexW3161389788

What OpenQuestion holds

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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.