A phase I‐<scp>II</scp> clinical trial of the anti‐<scp>CD</scp>74 monoclonal antibody milatuzumab in frail patients with refractory chronic lymphocytic leukaemia: <i>A patient based approach</i>

Haran, Michal; Mirkin, Vita; Braester, Andrei; Harpaz, N; Shevetz, Olga; Shtreiter, Marina; Greenberg, Shulamit; Mordich, Orly; Amram, Orna; Binsky-Ehrenreich, Inbal; Marom, Ayelet; Shachar, Idit; Herishanu, Yair; Ruchlemer, Rosa; Berrébi, Alain; Valinsky, Liora; Shtalrid, Mordechai; Shvidel, Lev

doi:10.1111/bjh.14726

Cited by 20 publications

(15 citation statements)

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“…Moreover, CD74 may even represent a protumorigenic signaling molecule in renal cell cancer (15). Milatuzumab, a CD74 antibody, is currently under clinical development and investigation for the treatment of various malignancies, such as multiple myeloma ( 55), lymphoma (11), and chronic lymphocytic leukemia (27). Thus, our study would also support a further evaluation of this drug as used in the treatment of ccRCC.…”

Section: Discussionmentioning

confidence: 73%

Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enables identification of molecular mechanisms

Koch

Finne

Eikrem

et al. 2019

American Journal of Physiology-Renal Physiology

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Renal cell cancer is among the most common forms of cancer in humans, with around 35,000 deaths attributed to kidney carcinoma in the European Union in 2012 alone. Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and the most lethal of all genitourinary cancers. Here, we apply omics technologies to archival core biopsies to investigate the biology underlying ccRCC. Knowledge of these underlying processes should be useful for the discovery and/or confirmation of novel therapeutic approaches and ccRCC biomarker development. From partial or full nephrectomies of 11 patients, paired core biopsies of ccRCC-affected tissue and adjacent (“peritumorous”) nontumor tissue were both sampled and subjected to proteomics analyses. We combined proteomics results with our published mRNA sequencing data from the same patients and with published miRNA sequencing data from an overlapping patient cohort from our institution. Statistical analysis and pathway analysis were performed with JMP Genomics and Ingenuity Pathway Analysis (IPA), respectively. Proteomics analysis confirmed the involvement of metabolism and oxidative stress-related pathways in ccRCC, whereas the most affected pathways in the mRNA sequencing data were related to the immune system. Unlike proteomics or mRNA sequencing alone, a combinatorial cross-omics pathway analysis approach captured a broad spectrum of biological processes underlying ccRCC, such as mitochondrial damage, repression of apoptosis, and immune system pathways. Sirtuins, immunoproteasome genes, and CD74 are proposed as potential targets for the treatment of ccRCC.

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Section: Discussionmentioning

confidence: 73%

Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enables identification of molecular mechanisms

Koch

Finne

Eikrem

et al. 2019

American Journal of Physiology-Renal Physiology

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“…An antibody targeting CD74 (Milatuzumab) underwent clinical trials (NCT00504972) and has been granted Orphan Drug Designation by the FDA for the treatment of CLL and multiple myeloma (197,198). A CXCR4 inhibitor was previously approved to mobilize hematopoietic cells for transplantation in patients with multiple myeloma and non-Hodgkin's lymphoma (199).…”

Section: Discussionmentioning

confidence: 99%

MIF-Dependent Control of Tumor Immunity

Noe

Mitchell

2020

Front. Immunol.

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Initially identified as a T lymphocyte-elicited inhibitor of macrophage motility, macrophage migration inhibitory factor (MIF) has since been found to be expressed by nearly every immune cell type examined and overexpressed in most solid and hematogenous malignant cancers. It is localized to both extracellular and intracellular compartments and physically interacts with more than a dozen different cell surface and intracellular proteins. Although classically associated with and characterized as a mediator of pro-inflammatory innate immune responses, more recent studies demonstrate that, in malignant disease settings, MIF contributes to anti-inflammatory, immune evasive, and immune tolerant phenotypes in both innate and adaptive immune cell types. This review will summarize the studies describing MIF in tumor-specific innate and adaptive immune responses and attempt to reconcile these various pleiotropic functions in normal physiology.

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“…In a similar manner, the use of MIF and DDT receptor antagonists could be considered when evaluating tailored MIF-DDT therapies for DMD. The anti-CD74 mAb milantuzumab is currently being studied in phase I/II studies for hematological cancers [55] and could represent a potential pharmacological candidate for MIF-DDT tailored interventions.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Involvement of the Macrophage Migration Inhibitory Factor Gene Network in Duchenne Muscular Dystrophy

Lombardo

Mazzon

Mangano

et al. 2019

Genes

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Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease with X-linked recessive inheritance, that leads patients to premature death. The loss of dystrophin determines membrane instability, causing cell damage and inflammatory response. Macrophage migration inhibitory factor (MIF) is a cytokine that exerts pleiotropic properties and is implicated in the pathogenesis of a variety of diseases. Recently, converging data from independent studies have pointed to a possible role of MIF in dystrophic muscle disorders, including DMD. In the present study, we have investigated the modulation of MIF and MIF-related genes in degenerative muscle disorders, by making use of publicly available whole-genome expression datasets. We show here a significant enrichment of MIF and related genes in muscle samples from DMD patients, as well as from patients suffering from Becker’s disease and limb-girdle muscular dystrophy type 2B. On the other hand, transcriptomic analysis of in vitro differentiated myotubes from healthy controls and DMD patients revealed no significant alteration in the expression levels of MIF-related genes. Finally, by analyzing DMD samples as a time series, we show that the modulation of the genes belonging to the MIF network is an early event in the DMD muscle and does not change with the increasing age of the patients, Overall, our analysis suggests that MIF may play a role in vivo during muscle degeneration, likely promoting inflammation and local microenvironment reaction.

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A phase I‐II clinical trial of the anti‐CD74 monoclonal antibody milatuzumab in frail patients with refractory chronic lymphocytic leukaemia: A patient based approach

Cited by 20 publications

References 10 publications

Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enables identification of molecular mechanisms

Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enables identification of molecular mechanisms

MIF-Dependent Control of Tumor Immunity

Transcriptomic Analysis Reveals Involvement of the Macrophage Migration Inhibitory Factor Gene Network in Duchenne Muscular Dystrophy

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