Evidence map›Paper›PMID 39043604›Full record

ArticleJournal for immunotherapy of cancer2024

Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma.

Jessica A Lake, Elena Woods, Eric Hoffmeyer, Kristin L Schaller, Joselyn Cruz-Cruz, Joseph Fernandez, Dejene Tufa, Benjamin Kooiman, Spencer C Hall, Dallas Jones and 2 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  13. Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

12 authors.

Jessica A LakeDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID http://orcid.org/0000-0001-7739-0850
Elena WoodsDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Eric HoffmeyerDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kristin L SchallerDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Joselyn Cruz-CruzDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Joseph FernandezDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Dejene TufaDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Benjamin KooimanDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Spencer C HallDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Dallas JonesDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Masanori HayashiDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Michael R VernerisDepartment of Pediatric Hematology, Oncology, BMT, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA MICHAEL.VERNERIS@CUANSCHUTZ.EDU.ORCID http://orcid.org/0000-0002-7097-5917

Funding

Cell Immunotherapy and Experimental Therapeutics Program (CIETP).T32CA236734 · NCI · UNIVERSITY OF COLORADO DENVER · PI Eduardo V Davila, Antonio Jimeno · 2019 to 2026
$2.0M
Multi-Modal Optical/ microCT system for Colorado Animal Imaging ResourceS10OD027023 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2020 to 2020
$733k
NCI NIH HHS T32 CA236734NIH HHS S10 OD027023
6 · The paper itself

Abstract

backgroundAdvances in pediatric oncology have occurred for some cancers; however, new therapies for sarcoma have been inadequate. Cellular immunotherapy using chimeric antigen receptor (CAR) T cells has shown dramatic benefits in leukemia, lymphoma, and multiple myeloma but has been far less successful in pediatric solid tumors such as rhabdomyosarcoma (RMS) and osteosarcoma (OS). Balancing issues of "on-target, off-tumor toxicity", investigators have identified B7-H3 as a broadly expressed tumor antigen with otherwise restricted expression on normal tissues. We hypothesized that rapid homing via a chemokine receptor and CAR engagement through B7-H3 would enhance CAR T cell efficacy in solid tumors.

methodsWe generated B7-H3 CAR T cells that also express the Interleukin-8 (IL-8) receptor, CXCR2. Cytokine production, flow cytometry, Seahorse assays and RNA sequencing were used to compare the B7-H3 CXCR2 (BC2) CAR T cells with B7-H3 CAR T cells. We developed an IL-8 overexpressing human RMS mouse model to test homing and cytotoxicity in vivo.

resultsWe demonstrate that IL-8 is expressed by RMS and OS and expression significantly increases after radiation. Overexpression of an IL-8 receptor, CXCR2, on B7-H3 CAR T cells enhances homing into IL-8 expressing tumors, augments T cell metabolism and leads to significant tumor regression.

conclusionThese findings warrant further investigation into the use of BC2 CAR T cells as a treatment for patients with RMS, OS and other B7-H3-expressing, IL-8 producing solid tumors.

Indexed as

B7 AntigensInterleukin-8Receptors, Chimeric AntigenAnimalsCell Line, TumorChildHumansImmunotherapy, AdoptiveMiceSarcomaT-LymphocytesXenograft Model Antitumor AssaysB7 AntigensCD276 protein, humanInterleukin-8Receptors, Chimeric AntigenAdoptive cell therapy - ACTChimeric antigen receptor - CARImmunotherapySolid tumor

Identifiers

PMID39043604
PMCPMC11268054

What OpenQuestion holds

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Registered trials

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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.