Evidence map›Paper›PMID 37199721›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023

Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases.

Olivia M Lucero, Ji-Ann Lee, Jenna Bowman, Kara Johnson, Gopal Sapparapu, John K Thomas, Guang Fan, Bill H Chang, Karina Thiel-Klare, Christopher A Eide and 7 more

Open access · greenAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Olivia M LuceroDepartment of Dermatology, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-6092-7025
Ji-Ann LeeClinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California.ORCID 0000-0002-9069-2113
Jenna BowmanKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0009-0007-7629-864X
Kara JohnsonKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0002-0993-4470
Gopal SapparapuClinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California.ORCID 0000-0001-9670-1757
John K ThomasClinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California.ORCID 0009-0004-2645-8316
Guang FanDepartment of Pathology and Clinical Laboratory Medicine, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0003-3827-4237
Bill H ChangKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0003-3783-1820
Karina Thiel-KlareDivision of Pediatric Hematology and Oncology, Oregon Health & Science University, Portland, Oregon.ORCID 0009-0004-6745-9681
Christopher A EideKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-8835-8928
Craig OkadaDivision of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon.ORCID 0009-0000-7061-0873
Mike PalazzoloClinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California.ORCID 0009-0008-5240-4396
Evan LindKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-7026-2012
Yoko KosakaKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0003-4811-099X
Brian J DrukerKnight Cancer Institute, Oregon Health & Science University, Portland, Oregon.ORCID 0000-0001-8331-8206
Nicholas LydonVB Therapeutics LLC, Jackson, Wyoming.ORCID 0009-0005-6041-1236
Peter M BowersTherapeutic Antibody Laboratory, Department of Pulmonology and Critical Care, David Geffen School of Medicine, Los Angeles, California.ORCID 0000-0002-4990-7100
Oregon Health & Science University · USSouthern California Clinical and Translational Science Institute · USUniversity of California System · USWyoming Game and Fish Department · US

Funding

Pathways of Immune Evasion in Acute Myeloid LeukemiaR01CA262145 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Evan Ferguson Lind · 2022 to 2026
$1.7M
NCI NIH HHS R01 CA262145
6 · The paper itself

Abstract

purposeTargeted therapeutics are a goal of medicine. Methods for targeting T-cell lymphoma lack specificity for the malignant cell, leading to elimination of healthy cells. The T-cell receptor (TCR) is designed for antigen recognition. T-cell malignancies expand from a single clone that expresses one of 48 TCR variable beta (Vβ) genes, providing a distinct therapeutic target. We hypothesized that a mAb that is exclusive to a specific Vβ would eliminate the malignant clone while having minimal effects on healthy T cells. EXPERIMENTAL

designWe identified a patient with large granular T-cell leukemia and sequenced his circulating T-cell population, 95% of which expressed Vβ13.3. We developed a panel of anti-Vβ13.3 antibodies to test for binding and elimination of the malignant T-cell clone.

resultsTherapeutic antibody candidates bound the malignant clone with high affinity. Antibodies killed engineered cell lines expressing the patient TCR Vβ13.3 by antibody-dependent cellular cytotoxicity and TCR-mediated activation-induced cell death, and exhibited specific killing of patient malignant T cells in combination with exogenous natural killer cells. EL4 cells expressing the patient's TCR Vβ13.3 were also killed by antibody administration in an in vivo murine model.

conclusionsThis approach serves as an outline for development of therapeutics that can treat clonal T-cell-based malignancies and potentially other T-cell-mediated diseases. See related commentary by Varma and Diefenbach, p. 4024.

Indexed as

Lymphoma, T-CellReceptors, Antigen, T-CellAnimalsHumansMiceReceptors, Antigen, T-Cell, alpha-betaRituximabT-LymphocytesReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaRituximab

Identifiers

PMID37199721
PMCPMC10592575
OpenAlexW4377010501

What OpenQuestion holds

Textmetadata
LicenceTDM
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.