Evidence map›Paper›PMID 42243894›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response.

Shahrzad Arya, Marco Ventin, Giulia Cattaneo, Martina Nebbia, Seyed Amir Sanatkar, Cristina Martin, Jingyu Jia, Bangjin Kim, Cedric A Bailey, Nabeel M Bardeesy and 6 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Shahrzad AryaDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marco VentinDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Giulia CattaneoDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Martina NebbiaDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Seyed Amir SanatkarDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cristina MartinDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jingyu JiaDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bangjin KimDepartment of Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Cedric A BaileyDepartment of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Nabeel M BardeesyMassGeneral Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David T TingMassGeneral Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Vikram DeshpandeDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Xinhui WangDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sandra RyeomDepartment of Surgery, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
Soldano FerroneDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cristina R FerroneDepartment of Surgery, Division of Gastrointestinal and Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. cristina.ferrone@csmc.edu.

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2M
Functions of mutant IDH in cholangiocarcinomaR01CA280085 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NABEEL El-BARDEESY · 2023 to 2026
$2.6M
Harnessing mutant IDH1 as a therapeutic target in liver cancer and other solid malignanciesR01CA292508 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NABEEL El-BARDEESY, Robert Thomas Manguso · 2025 to 2026
$1.4M
Cholangiocarcinoma Foundation Award AstraZeneca/CCF Research Fellowship AWD00001136Department of Defense Award HT9425-23-1-0886NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA280085NCI NIH HHS R01 CA292508The Dana-Faber/Harvard Cancer Center (DF/HCC) SPORE grant in Gastrointestinal Cancer P50CA127003
6 · The paper itself

Abstract

backgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor, with an increasing incidence over the past two decades. While surgery offers a curative option, most patients present with advanced disease, for which current therapeutic options are ineffective. B7-H3 is an immune checkpoint molecule that is overexpressed in ICC relative to normal tissue, making it an attractive therapeutic target. Utilizing in vitro and in vivo models, we investigated the efficacy of a B7-H3-targeted CAR T to treat ICC.

methodsB7-H3 CAR T cells were generated from peripheral blood mononuclear cells of normal donors, transduced with a retroviral vector encoding a second generation B7-H3 specific CAR construct, incorporating an inducible caspase9 (iCas9) suicide gene-based safety switch. The anti-tumor activity of iCas9.B7-H3 CAR T cells against ICC was tested in vitro using human ICC cell lines and patient-derived organotypic tumor spheroids (PDOTS) and in vivo using xenograft models of ICC.

resultsHuman ICC cell lines, resected ICC samples from patients, and ICC tissue microarrays demonstrate homogeneous expression of B7-H3. iCas9.B7-H3 CAR T cells demonstrated potent anti-tumor activity in vitro against multiple patient-derived ICC cell lines. A single systemic dose of iCas9.B7-H3 CAR T cells induced complete and sustained eradication of orthotopic ICC tumors in a preclinical mouse model, even after tumor re-challenge. Locoregional delivery of CAR T cells via splenic and intra-tumoral injection was equally effective as systemic therapy.

conclusionsThese results provide a strong rationale for evaluating the iCas9.B7-H3 CAR T cell strategy in clinical trials for patients with advanced ICC.

Indexed as

B7 AntigensBile Duct NeoplasmsCholangiocarcinomaImmunotherapy, AdoptiveReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorHumansMiceXenograft Model Antitumor AssaysB7 AntigensCD276 protein, humanReceptors, Chimeric AntigenB7-H3CAR T cellsChimeric antigen receptorImmunotherapyIntrahepatic cholangiocarcinoma

Identifiers

PMID42243894
PMCPMC13255452

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.