Evidence map›Paper›PMID 41469141›Full record

ArticleJournal for immunotherapy of cancer2025

Affinity-matured CD72-targeting nanobody CAR T cells enhance elimination of antigen-low B-cell malignancies.

Adila Izgutdina, Tasfia Rashid, William C Temple, Sarah Aminov, Bonell Patiño-Escobar, Sujata Walunj, Huimin Geng, Hiroyuki Takamatsu, Daniel Gil-Alós, Amrik S Kang and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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.

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

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Adila IzgutdinaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0002-3296-3261
Tasfia RashidDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
William C TempleDepartment of Pediatrics, Division of Oncology, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0003-3375-2703
Sarah AminovDepartment of Oncology, Blood Cancer Institute, Albert Einstein College of Medicine, Bronx, New York, USA.
Bonell Patiño-EscobarDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Sujata WalunjDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Huimin GengDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Hiroyuki TakamatsuDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Daniel Gil-AlósDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Amrik S KangDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Emilio RamosDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Szu-Ying ChenDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Haley JohnsonDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Matthew A NixDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Akul NaikDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Mingcheng LiDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA.
Constance M YuanLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Hao-Wei WangLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Srabani SahuDepartment of Oncology, Blood Cancer Institute, Albert Einstein College of Medicine, Bronx, New York, USA.
Rebecca C LarsonCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0003-0174-061X
Christopher CarpenterArc Institute, Palo Alto, California, USA.
Fernando SalangsangPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Paul PhojanakongPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Juan Antonio Camara SerranoPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Isa TariqPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Ons ZakraouiPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Veronica SteriPreclinical Therapeutics Core, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Antonio ValeriHospital Universitario 12 de Octubre-Centro Nacional de Investigaciones Oncológicas (H12O-CNIO) Haematological Malignancies Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain.
Joaquin Martinez-LopezHospital Universitario 12 de Octubre-Centro Nacional de Investigaciones Oncológicas (H12O-CNIO) Haematological Malignancies Clinical Research Unit, Spanish National Cancer Research Centre, Madrid, Spain.
Marcela V MausCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0002-7578-0393
Samir ParekhDepartment of Medicine, Division of Hematology and Medical Oncology; Department of Oncological Sciences; and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Amit VermaDepartment of Oncology, Blood Cancer Institute, Albert Einstein College of Medicine, Bronx, New York, USA.
Nirali N ShahPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-8474-9080
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA arun.wiita@ucsf.edu.ORCID http://orcid.org/0000-0002-7465-6964

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Medical Scientist Training Program (T32 NRSA Training Grant)T32GM141323 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Aimee Kao · 2021 to 2026
$10.5M
TRAINING IN TRANSPLANTATION BIOLOGYT32AI007529 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI MADSEN, JOREN C · 1998 to 2024
$6.4M
Immunotherapeutic approaches to treat pediatric hematologic malignanciesZIABC011823 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHAH, NIRALI · 2019 to 2025
$6.1M
Intramural NIH HHS ZIA BC011823NCI NIH HHS P30 CA082103NIAID NIH HHS T32 AI007529NIGMS NIH HHS T32 GM141323
6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR) T-cell therapies are highly efficacious for several different hematologic cancers. However, for most CAR T targets it is observed that low surface antigen density on tumors can significantly reduce therapeutic efficacy. In this study, we explore this dynamic in the context of CD72, a surface antigen we recently found as a promising target for refractory B-cell cancers, but for which CD72 low antigen density can lead to therapeutic resistance in preclinical models.

methodsPrimary samples were accessed via institutional review board-approved protocols. Affinity-matured and humanized nanobody clones were previously described in Temple

resultsWe first confirmed ubiquitous CD72 expression across a range of primary B-cell non-Hodgkin lymphomas. We further found that after resistance to CD19-directed therapies, across both B-cell acute lymphoblastic leukemia (B-ALL) models and primary tumor samples, surface CD72 expression was largely preserved while CD22 expression was significantly diminished. Affinity maturation of a nanobody targeting CD72, when incorporated into CAR T cells, led to more effective elimination in vitro of isogenic models of CD72 low-expressing tumors. These results suggested that nanobody-based CAR T cells (nanoCARs) may exhibit a similar relationship between binder affinity, antigen expression, and efficacy as previously demonstrated only for single chain variable fragment-based CAR T cells. Surprisingly, however, this significantly improved in vitro efficacy only translated to modest in vivo survival benefit. As a parallel strategy to enhance CAR T function, we found that the small molecule bryostatin could also significantly increase CD72 surface antigen density on B-cell malignancy models. Structural modeling and biochemical analysis identified critical residues improving CD72 antigen recognition of our lead affinity-matured nanobody.

conclusionsTogether, these findings support affinity-matured CD72 nanoCARs as a potential immunotherapy product for CD19-refractory B-cell cancers. Our results also suggest that for B-ALL in particular, CD72 may be a preferable second-line immunotherapy target over CD22.

Indexed as

Antigens, CDAntigens, Differentiation, B-LymphocyteImmunotherapy, AdoptiveLymphoma, B-CellReceptors, Chimeric AntigenSingle-Domain AntibodiesAnimalsCell Line, TumorHumansMiceMice, Inbred NODMice, SCIDXenograft Model Antitumor AssaysAntigens, CDAntigens, Differentiation, B-LymphocyteReceptors, Chimeric AntigenSingle-Domain AntibodiesChimeric antigen receptor - CARImmunotherapyLeukemiaLYMPHOMA

Identifiers

PMID41469141
PMCPMC12766774

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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.