Evidence map›Paper›PMID 39794935›Full record

ArticleJournal for immunotherapy of cancer2024

GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.

Khalid A Mohamedali, Brian Aguirre, Cheng-Hsiang Lu, Anubhav Chandla, Nidhi Kejriwal, Lucia Liu, Ann M Chan, Lawrence H Cheung, SuYin Kok, Sergio Duarte and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Article
  3. Single-cell transcriptome analysis identifies subclusters and signature with N-glycosylation in endometrial cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  4. Targeted intervention in obesity-associated atrial fibrosis using nanoparticle-loaded fusion protein.Apoptosis : an international journal on programmed cell death · 2025
    Article
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

14 authors.

Khalid A MohamedaliExperimental Therapeutics, University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA.ORCID 0000-0002-8249-5304
Brian AguirreDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Cheng-Hsiang LuWidjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Anubhav ChandlaDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.ORCID 0009-0001-3999-8811
Nidhi KejriwalDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Lucia LiuDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Ann M ChanDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Lawrence H CheungExperimental Therapeutics, University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA.
SuYin KokDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA.
Sergio DuarteDepartment of Surgery, University of California Los Angeles, Los Angeles, California, USA.
Ana Alvarez de CienfuegosExperimental Therapeutics, University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA.ORCID 0000-0002-6427-5447
David CaseroWidjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.ORCID 0000-0002-7347-3330
Michael G RosenblumExperimental Therapeutics, University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, USA.
Madhuri WadehraDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California, USA mwadehra@mednet.ucla.edu.ORCID 0000-0001-8514-2021

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGranzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. Fusion proteins and immunoconjugates represent an innovative therapeutic approach to specifically deliver a deadly payload to target cells. Epithelial membrane protein-2 (EMP2) is highly expressed in invasive breast cancer (BC), including triple-negative BC (TNBC), and represents an attractive therapeutic target.

methodsWe designed a novel fusion protein (GrB-Fc-KS49) composed of an active GrB fused to an anti-EMP2 single-chain antibody tethered through the immunoglobulin G heavy chain (Fc) domain. We assessed the construct's GrB enzymatic activity, anti-EMP2 binding affinity, and cytotoxicity against a panel of BC cells. The construct's pharmacokinetics (PK), toxicity profile, and in vivo efficacy were also evaluated.

resultsGrB-Fc-KS49 exhibited comparable GrB enzymatic activity to commercial GrB, as well as high affinity to an EMP2 peptide, with the dissociation constant in the picomolar range. The fusion protein rapidly internalized into EMP2+cancer cells and showed in vitro cytotoxicity to cell lines expressing surface EMP2, with half-maximal cytotoxicity (IC

conclusionsGrB-Fc-KS49 showed high specificity and cytotoxicity towards EMP2-positive cells. In vivo, it reduced tumor burden and increased the recruitment of immune cells into the tumor, suggesting that GrB-Fc-KS49 is a promising therapeutic candidate against BC.

Indexed as

Breast NeoplasmsGranzymesRecombinant Fusion ProteinsAnimalsCell Line, TumorCell ProliferationFemaleHumansMiceXenograft Model Antitumor AssaysGranzymesRecombinant Fusion ProteinsBreast CancerTumor microenvironment - TME

Identifiers

PMID39794935
PMCPMC11667298

What OpenQuestion holds

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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.