Evidence map›Paper›PMID 27119093›Full record

ArticleMolecular therapy oncolytics2014

Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor.

Agnes Shuk-Yee Lo, Chen Xu, Akikazu Murakami, Wayne A Marasco

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy oncolytics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

12 citing papers in PubMed, 25 citations in OpenAlex.

  1. CAR-T Cell Therapy: Advances in Kidney-Related Diseases.Kidney diseases (Basel, Switzerland) · 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

4 authors at 3 institutions in 2 countries.

Agnes Shuk-Yee LoDepartment of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Chen XuDepartment of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Beijing Tri-Prime Genetic Engineering Co., Ltd, Beijing, P.R. China.
Akikazu MurakamiDepartment of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Department of Parasitology & Immunopathoetiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Wayne A MarascoDepartment of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USDana-Farber Cancer Institute · USUniversity of the Ryukyus · JP

Funding

Genetic Retargeted Human T-cells for RCC ImmunotherapyR21DK072282 · NIDDK · DANA-FARBER CANCER INSTITUTE · PI MARASCO, WAYNE A. · 2005 to 2006
$458k
NIDDK NIH HHS R21 DK072282
6 · The paper itself

Abstract

Carbonic anhydrase IX (CAIX) is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC) but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs) that utilize a carbonic anhydrase (CA) domain mapped, human single chain antibody (scFv G36) as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells) expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX(+) RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL)-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX(+) RCC.

Identifiers

PMID27119093
PMCPMC4782938
OpenAlexW2328430079

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.