Evidence map›Paper›PMID 38867077›Full record

ArticleNature medicine2024

PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.

Tanya B Dorff, M Suzette Blanchard, Lauren N Adkins, Laura Luebbert, Neena Leggett, Stephanie N Shishido, Alan Macias, Marissa M Del Real, Gaurav Dhapola, Colt Egelston and 18 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03873805 (A Phase I Study to Evaluate PSCA-Targeting Chimeric Antigen Receptor), which is not on this map. Cited by 90 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 5 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.

NCT03873805 phase1active not recruitingnot on this map

A Phase I Study to Evaluate PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer

TypeinterventionalSponsorCity of Hope Medical CenterRan2019 to 2027Enrolled14ConditionsCastration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8ArmsAutologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes, Cyclophosphamide, Fludarabine, Fludarabine Phosphate
3 · Its place in the literature

Who cites it

90 citing papers in PubMed, 5 syntheses or guidelines pooled it.

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  20. Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026
    Review

30 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

28 authors.

Tanya B DorffDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA. tdorff@coh.org.ORCID 0000-0001-5990-298X
M Suzette BlanchardDepartment of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
Lauren N AdkinsDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Laura LuebbertDepartments of Mathematics and Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Neena LeggettDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Stephanie N ShishidoMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, University of Southern California, Los Angeles, CA, USA.
Alan MaciasDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Marissa M Del RealDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Gaurav DhapolaDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Colt EgelstonDepartment of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, USA.
John P MuradDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.ORCID 0000-0003-0637-2414
Reginaldo RosaDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.ORCID 0000-0003-0984-8959
Jinny PaulDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Ammar ChaudhryDepartment of Radiology, City of Hope, Duarte, CA, USA.
Hripsime MartirosyanDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Ethan GerdtsDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Jamie R WagnerDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Tracey StillerDepartment of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
Dileshni TilakawardaneDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
Sumanta PalDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.ORCID 0000-0002-1712-0848
Catalina MartinezDepartment of Clinical and Translational Project Development, City of Hope, Duarte, CA, USA.
Robert E ReiterDepartment of Urology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
Lihua E BuddeDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.ORCID 0000-0003-1464-5494
Massimo D'ApuzzoDepartment of Pathology, City of Hope, Duarte, CA, USA.ORCID 0000-0001-8146-0997
Peter KuhnMichelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, University of Southern California, Los Angeles, CA, USA.
Lior PachterDepartments of Mathematics and Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Stephen J FormanDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.ORCID 0000-0002-2803-4152
Saul J PricemanDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA. spriceman@coh.org.ORCID 0000-0002-8136-2112

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
NCI NIH HHS P30 CA033572NCI NIH HHS P50 CA092131Prostate Cancer Foundation (PCF) 2017 challenge awardProstate Cancer Foundation (PCF) challenge award
6 · The paper itself

Abstract

Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The starting dose level (DL) was 100 million (M) CAR T cells without lymphodepletion (LD), followed by incorporation of LD. The primary end points were safety and dose-limiting toxicities (DLTs). No DLTs were observed at DL1, with a DLT of grade 3 cystitis encountered at DL2, resulting in addition of a new cohort using a reduced LD regimen + 100 M CAR T cells (DL3). No DLTs were observed in DL3. Cytokine release syndrome of grade 1 or 2 occurred in 5 of 14 treated patients. Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements. Dynamic changes indicating activation of peripheral blood endogenous and CAR T cell subsets, TCR repertoire diversity and changes in the tumor immune microenvironment were observed in a subset of patients. Limited persistence of CAR T cells was observed beyond 28 days post-infusion. These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 .

Indexed as

Antigens, NeoplasmGPI-Linked ProteinsImmunotherapy, AdoptiveNeoplasm ProteinsProstatic Neoplasms, Castration-ResistantAgedHumansMaleMiddle AgedNeoplasm MetastasisProstate-Specific AntigenReceptors, Chimeric AntigenT-LymphocytesAntigens, NeoplasmGPI-Linked ProteinsNeoplasm ProteinsProstate-Specific AntigenPSCA protein, humanReceptors, Chimeric Antigen

Identifiers

PMID38867077
PMCPMC11186768

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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.