CD64-directed microtubule associated protein tau kills leukemic blasts<i>ex vivo</i>

Mladenov, Radoslav; Hristodorov, Dmitrij; Cremer, Christian; Gresch, Gerrit; Grieger, Elena; Schenke, Lea; Klose, Diana; Amoury, Manal; Woitok, Mira; Jost, Edgar; Brümmendorf, Tim H.; Fendel, Rolf; Fischer, Rainer; Stein, Christoph; Thepen, Theo; Barth, Stefan

doi:10.18632/oncotarget.11568

Cited by 12 publications

(11 citation statements)

References 42 publications

(55 reference statements)

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“…Human microtubule-associated protein tau (MAP tau) belongs to a group of microtubule targeting agents capable of inducing apoptosis in rapidly proliferating cancer cells [ 81 ]. To induce apoptosis, recombinant MAP tau binds to microtubule binding repeats on microtubules and by so doing, irreversibly enhance the polymerization of microtubules in a process that halts cell division and induces apoptosis in target cells [ 82 ]. Indeed, agents that target the mitotic phase of cell division to induce cell death have been the most successful in the treatment of cancer [ 83 ].…”

Section: Cd64 Based Immunotherapeutic Studies In Chronic Inflammatmentioning

confidence: 99%

CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

et al. 2017

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To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64) have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

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Section: Cd64 Based Immunotherapeutic Studies In Chronic Inflammatmentioning

confidence: 99%

CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

et al. 2017

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“…On top of that, ex vivo data demonstrated that H22(scFv)–MAP efficiently recognizes CD64 + leukemic blasts, leading to their elimination, while it spares the homeostasis of healthy CD64 + PBMC. The same study showed the ability of the human cytolytic fusion protein to kill leukemic cells independently of the target receptor profile, which suggests the high potency of MAP tau as cytostatic agent [ 64 ]. In the context of leukaemia, similar results on the efficacy of MAP tau were obtained when evaluating CD89 as a target for immunotherapy [ 69 ].…”

Section: Microtubule Associated Protein (Map) Tau: Discovery and Smentioning

confidence: 99%

Human MAP Tau Based Targeted Cytolytic Fusion Proteins

et al. 2017

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Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g., auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested in identifying a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau), which binds specifically to tubulin and modulates the stability of microtubules, thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g., cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

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“…FCGR1A has a pivotal role in chronic inflammatory diseases and in response to infections 42 , 43 . Moreover, FCGR1 protein activates the phagocytic activity of myeloid-cells, inducing antitumoral activity 44 , 45 . Interestingly, the binding receptor, the Fc fragment of γ immunoglobulin, could also influence the anti-tumor activity of antibodies against immune checkpoint targets 46 .…”

Section: Discussionmentioning

confidence: 99%

A role for the immune system in advanced laryngeal cancer

Tagliabue

Maffini

Fumagalli

et al. 2020

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To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p < 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients’ immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy.

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CD64-directed microtubule associated protein tau kills leukemic blastsex vivo

Cited by 12 publications

References 42 publications

CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

Human MAP Tau Based Targeted Cytolytic Fusion Proteins

A role for the immune system in advanced laryngeal cancer

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