Related Experiment Video
Updated: Jul 30, 2026
Generation of Human CD40-activated B cells
Published on: October 16, 2009
Preclinical in vitro and in vivo evidence for targeting CD74 as an effective treatment strategy for cutaneous T-cell
Mariantonia Costanza1,2,3, Catello Giordano, Ann-Christin von Brünneck
1Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Biology of Malignant Lymphomas, Berlin, Germany.
Background:
Prognosis and quality of life in patients with advanced cutaneous T-cell lymphoma (CTCL), particularly in those with Sézary syndrome (SS) or advanced-stage mycosis fungoides (MF), are poor. Monoclonal antibodies or antibody-drug conjugates (ADCs) have been added into CTCL treatment algorithms, but the spectrum of antibody-targetable cell surface antigens in T-cell non-Hodgkin lymphomas (T-NHLs) is limited.
Objectives:
To evaluate the expression of the major histocompatibility complex class II chaperone CD74 in common subtypes of CTCL by various methods, and to explore the efficacy of targeting CD74 in CTCL cells with an anti-CD74 ADC in vitro and in vivo.
Methods:
We comprehensively investigated the expression of CD74 in well-defined CTCL cell lines by polymerase chain reaction, immunoblotting and flow cytometry. More than 140 primary CTCL samples of all common subtypes were analysed by immunohistochemistry, flow cytometry, immunofluorescence and 'co-detection by indexing' (CODEX) multiplexed tissue imaging, as well as by single-cell RNA sequencing (scRNAseq) analyses. DNA methylation of CTCL cell lines was interrogated by the generation of genome-wide methylation profiling. The effect of a maytansinoid-conjugated humanized ADC against CD74 was investigated in CTCL cell lines in vitro, alone or in combination with gemcitabine, and in vivo after xenotransplantation of CTCL cell lines in NOD-scid Il2rgnull mice.
Results:
We demonstrated that CD74 is widely and robustly expressed in CTCL cells. In addition, CD74 expression in SS and MF was confirmed by scRNAseq data analysis and was correlated in CTCL cell lines with CD74 DNA hypomethylation. CD74 was rapidly internalized in CTCL cells and CD74 targeting by the ADC STRO-001 efficiently killed CTCL-derived cell lines. Finally, targeting of CD74 synergized with conventional chemotherapy in vitro and eradicated murine xenotransplants of CTCL cell lines in vivo.
Conclusions:
CD74 is expressed in common CTCL subtypes. Targeting CD74 efficiently killed CTCL cells in vitro and in vivo. We therefore suggest the targeting of CD74 to be a highly promising treatment strategy for CTCL.
Insights
Targeting CD74, a protein widely expressed in cutaneous T-cell lymphoma (CTCL), shows promise for treating this condition. An antibody-drug conjugate (ADC) targeting CD74 effectively killed CTCL cells in vitro and in vivo, suggesting a new therapeutic strategy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Advanced cutaneous T-cell lymphoma (CTCL), including Sézary syndrome (SS) and mycosis fungoides (MF), has a poor prognosis.
- Current treatment options for CTCL are limited by a narrow range of targetable cell surface antigens for monoclonal antibodies and antibody-drug conjugates (ADCs).
Purpose of the Study:
- To evaluate the expression of CD74, a major histocompatibility complex class II chaperone, in common CTCL subtypes.
- To investigate the efficacy of targeting CD74 with an anti-CD74 ADC in CTCL cells both in vitro and in vivo.
Main Methods:
- Comprehensive analysis of CD74 expression in CTCL cell lines and over 140 primary CTCL samples using various techniques including PCR, immunoblotting, flow cytometry, CODEX multiplexed imaging, and scRNAseq.
- Investigation of CD74 DNA methylation in CTCL cell lines.
- In vitro and in vivo assessment of an anti-CD74 ADC (STRO-001) efficacy, alone and in combination with gemcitabine.
Main Results:
- CD74 was found to be widely and robustly expressed across common CTCL subtypes, including SS and MF.
- CD74 expression correlated with CD74 DNA hypomethylation in CTCL cell lines and showed rapid internalization upon targeting.
- The anti-CD74 ADC (STRO-001) demonstrated efficient killing of CTCL cell lines in vitro, synergized with chemotherapy, and eradicated xenotransplants in vivo.
Conclusions:
- CD74 is a consistently expressed target in common CTCL subtypes.
- Targeting CD74 with an ADC proved effective in eliminating CTCL cells in both laboratory and animal models.
- Targeting CD74 represents a highly promising therapeutic strategy for patients with CTCL.
Related Concept Videos
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
01:27Tumor Immunotherapy