Evidence map›Paper›PMID 32381575›Full record

ArticleHaematologica2021

CD28.OX40 co-stimulatory combination is associated with long in vivo persistence and high activity of CAR.CD30 T-cells.

Marika Guercio, Domenico Orlando, Stefano Di Cecca, Matilde Sinibaldi, Iolanda Boffa, Simona Caruso, Zeinab Abbaszadeh, Antonio Camera, Biancamaria Cembrola, Katia Bovetti and 20 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.0field-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

46 citing papers in PubMed, 69 citations in OpenAlex.

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  16. GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

30 authors at 2 institutions in 1 country.

Marika GuercioDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Domenico OrlandoDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Stefano Di CeccaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Matilde SinibaldiDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Iolanda BoffaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Simona CarusoDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Zeinab AbbaszadehDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Antonio CameraDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Biancamaria CembrolaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Katia BovettiDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Simona ManniDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Ignazio CaruanaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Roselia CicconeDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Francesca Del BufaloDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Pietro MerliDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Luciana VintiDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Katia GirardiDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Annalisa RuggeriDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Cristiano De StefanisDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Marco PezzulloDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Ezio GiordaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Marco ScarsellaDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Rita De VitoDept. of Laboratories, Pathology Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
Sabina BarresiGenetics and Rare Diseases Research Div, Ospedale Pediatrico Bambino Gesù IRCSS, Rome, Italy.
Andrea CiolfiGenetics and Rare Diseases Research Div, Ospedale Pediatrico Bambino Gesù IRCSS, Rome, Italy.
Marco TartagliaGenetics and Rare Diseases Research Div, Ospedale Pediatrico Bambino Gesù IRCSS, Rome, Italy.
Lorenzo MorettaDepartment of Immunology, Bambino Gesù Children Hospital, IRCCS, Rome, Rome, Italy.
Franco LocatelliDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Concetta QuintarelliDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Biagio De AngelisDept Onco-Haematology, Cell and Gene Therapy, Bambino Gesù Children Hospital, Rome, Italy.
Bambino Gesù Children's Hospital · ITIstituti di Ricovero e Cura a Carattere Scientifico · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The prognosis of many patients with chemotherapy-refractory or multiply relapsed CD30+ non-Hodgkin Lymphoma (NHL) or Hodgkin lymphoma (HL) still remains poor, and novel therapeutic approaches are warranted to address this unmet clinical need. In light of this consideration, we designed and pre-clinically validated a Chimeric Antigen Receptor (CAR) construct characterized by a novel anti-CD30 single-chain variable-fragment cassette, linked to CD3ζ by the signaling domains of two costimulatory molecules, namely either CD28.4-1BB or CD28.OX40. We found that CAR.CD30 T-cells exhibit remarkable cytolytic activity in vitro against HL and NHL cell lines, with sustained proliferation and pro-inflammatory cytokine production, even after multiple and sequential lymphoma cell challenges. CAR.CD30 T-cells also demonstrated anti-lymphoma activity in two in vivo xenograft immune-deficient mouse models of metastatic HL and NHL. We observed that administration of CAR.CD30 T-cells, incorporating the CD28.OX40 costimulatory domains and manufactured in the presence of IL7 and IL15, were associated with the best overall survival in the treated mice, along with the establishment of a long-term immunological memory, able to protect mice from further tumor re-challenge. Our data indicate that, in the context of in vivo systemic metastatic xenograft mouse models, the costimulatory machinery of CD28.OX40 is crucial for improving persistence, in vivo expansion and proliferation of CAR.CD30 T-cells upon tumor encounter. CD28.OX40 costimulatory combination is ultimately responsible for the antitumor efficacy of the approach, paving the way to translate this therapeutic strategy in patients with CD30+ HL and NHL.

Indexed as

CD28 AntigensReceptors, Chimeric AntigenAnimalsHumansImmunotherapy, AdoptiveMiceReceptors, Antigen, T-CellT-LymphocytesCD28 AntigensReceptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID32381575
PMCPMC8018158
OpenAlexW3022991438

What OpenQuestion holds

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LicenceCC BY-NC
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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.