Evidence map›Paper›PMID 35570396›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Locally secreted BiTEs complement CAR T cells by enhancing killing of antigen heterogeneous solid tumors.

Yibo Yin, Jesse L Rodriguez, Nannan Li, Radhika Thokala, MacLean P Nasrallah, Li Hu, Logan Zhang, Jiasi Vicky Zhang, Meghan T Logun, Devneet Kainth and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% 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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Pooled it
  2. Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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15 more citing papers are in PubMed but not listed here.

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

21 authors at 2 institutions in 2 countries.

Yibo YinDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Center for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jesse L RodriguezCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nannan LiDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Center for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Radhika ThokalaCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
MacLean P NasrallahGBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Li HuDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Logan ZhangCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jiasi Vicky ZhangCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Meghan T LogunCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Devneet KainthCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Leila HaddadCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yang ZhaoDepartment of Operating Room, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Tong WuDepartment of Ultrasound, Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Emily X JohnsCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yu LongDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Hongsheng LiangDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Jiping QiDepartment of Pathology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Xiangtong ZhangDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Zev A BinderCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhiguo LinDepartment of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. Electronic address: linzhiguo@hotmail.com.
Donald M O'RourkeCenter for Cellular Immunotherapies, University of Pennsylvania Philadelphia, PA 19104, USA; GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: donald.orourke@pennmedicine.upenn.edu.
University of Pennsylvania · USHarbin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific T cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III, and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the single chain variable fragments to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE-secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long term. In summary, BiTEs secreted by mono- or multi-valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.

Indexed as

GlioblastomaInterleukin-13 Receptor alpha2 SubunitAnimalsCell Line, TumorErbB ReceptorsImmunotherapy, AdoptiveMiceT-LymphocytesXenograft Model Antitumor AssaysErbB ReceptorsInterleukin-13 Receptor alpha2 Subunitbispecific T cell engagerchimeric antigen receptorEGFRglioblastomagliomaIL13Ra2

Identifiers

PMID35570396
PMCPMC9263323
OpenAlexW4280516111

What Socratic 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 Socratic graph.