Evidence map›Paper›PMID 28805662›Full record

ArticleThe Journal of clinical investigation2017

Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes.

Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley and 7 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01316146 (Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma), which is not on this map. Cited by 229 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
229citing papers in PubMed, 2 pooled it
20.3field-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.

NCT01316146 phase1withdrawnnot on this map

Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma (CART CD30)

TypeinterventionalSponsorUNC Lineberger Comprehensive Cancer CenterRan2011 to 2022Enrolled0ConditionsNon-Hodgkin's Lymphoma, Hodgkin's LymphomaArmsCAR.CD30 T cells
3 · Its place in the literature

Who cites it

229 citing papers in PubMed, 2 syntheses or guidelines pooled it, 366 citations in OpenAlex.

  1. Pooled it
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  8. Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
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169 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

17 authors at 5 institutions in 1 country.

Carlos A RamosCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Brandon BallardCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Huimin ZhangCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Olga DakhovaCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Adrian P GeeCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Zhuyong MeiCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Mrinalini BilgiCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Meng-Fen WuBiostatistics Shared Resource, Dan L. Duncan Cancer Center, and.
Hao LiuDepartment of Medicine.
Bambi GrilleyCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Catherine M BollardCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Bill H ChangDivision of Pediatric Hematology and Oncology, Oregon Health and Science University, Portland, Oregon, USA.
Cliona M RooneyCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Malcolm K BrennerCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Helen E HeslopCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Gianpietro DottiCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Barbara SavoldoCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas, USA.
Baylor College of Medicine · USHouston Methodist · USTexas Children's Hospital · USDan L Duncan Comprehensive Cancer CenterMethodist Hospital · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Tissue ResourceP50CA126752 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, HELEN E HESLOP · 2007 to 2026
$51.4M
Enhancement of stem cell transplants using CAR.CD30-redirected T lymphocytesR01HL114564 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SAVOLDO, BARBARA · 2013 to 2017
$2.2M
Chimeric T Cell for Therpay of Hodgkin DiseaseR01CA131027 · NCI · BAYLOR COLLEGE OF MEDICINE · PI SAVOLDO, BARBARA · 2008 to 2012
$1.6M
NCI NIH HHS P30 CA016086NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA126752NCI NIH HHS R01 CA131027NHLBI NIH HHS R01 HL114564
6 · The paper itself

Abstract

backgroundTargeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity.

methodsWe conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30.CAR-Ts) encoding the CD28 costimulatory endodomain. Three dose levels, from 0.2 × 108 to 2 × 108 CD30.CAR-Ts/m2, were infused without a conditioning regimen. All other therapy for malignancy was discontinued at least 4 weeks before CD30.CAR-T infusion. Seven patients had previously experienced disease progression while being treated with brentuximab.

resultsNo toxicities attributable to CD30.CAR-Ts were observed. Of 7 patients with relapsed HL, 1 entered complete response (CR) lasting more than 2.5 years after the second infusion of CD30.CAR-Ts, 1 remained in continued CR for almost 2 years, and 3 had transient stable disease. Of 2 patients with ALCL, 1 had a CR that persisted 9 months after the fourth infusion of CD30.CAR-Ts. CD30.CAR-T expansion in peripheral blood peaked 1 week after infusion, and CD30.CAR-Ts remained detectable for over 6 weeks. Although CD30 may also be expressed by normal activated T cells, no patients developed impaired virus-specific immunity.

conclusionCD30.CAR-Ts are safe and can lead to clinical responses in patients with HL and ALCL, indicating that further assessment of this therapy is warranted.

trial registrationClinicalTrials.gov NCT01316146.

fundingNational Cancer Institute (3P50CA126752, R01CA131027 and P30CA125123), National Heart, Lung, and Blood Institute (R01HL114564), and Leukemia and Lymphoma Society (LLSTR 6227-08).

Indexed as

AdultAntineoplastic AgentsBrentuximab VedotinCD28 AntigensDisease ProgressionDose-Response Relationship, DrugFemaleHodgkin DiseaseHumansImmunoconjugatesImmunophenotypingKi-1 AntigenLymphoma, Large-Cell, AnaplasticMaleMiddle AgedMolecular Targeted TherapyAntineoplastic AgentsBrentuximab VedotinCD28 AntigensImmunoconjugatesKi-1 AntigenReceptors, Antigen, T-Cell

Identifiers

PMID28805662
PMCPMC5669573
OpenAlexW2743083943

What OpenQuestion holds

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Registered trials

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.