The Effect of GM-CSF to Preventing Oral Mucositis for Patients With Nasopharyngeal Carcinoma Receiving Radiotherapy: A Single-center, Phase II, Randomized Trial

To evaluate the efficacy of GM-CSF to preventing oral mucositis for patients with nasopharyngeal carcinoma receiving radiotherapy.

Start Date15 Sep 2023

Sponsor / Collaborator

Sun Yat-Sen University

100 Clinical Results associated with GM-CSF(Sun Yat-sen University)

100 Translational Medicine associated with GM-CSF(Sun Yat-sen University)

100 Patents (Medical) associated with GM-CSF(Sun Yat-sen University)

1,062

Literatures (Medical) associated with GM-CSF(Sun Yat-sen University)

01 Feb 2025·Scandinavian Journal of Immunology

The impact of cytokines and tumour‐conditioned medium on the properties of murine in vitro generated myeloid‐derived suppressor cells

Article

Author: Awad, Mona ; Markov, Oleg ; Sen'kova, Aleksandra ; Zenkova, Marina

AbstractMyeloid‐derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells playing a critical role in immune suppression. In vitro‐generated MDSCs are a convenient tool to study the properties of tumour‐associated MDSCs. Here, we compared six protocols for in vitro generation of functional mouse MDSCs from bone marrow progenitors. The protocols included granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) alone or in combination with interleukin‐6 (IL‐6) or granulocyte colony‐stimulating factor (G‐CSF), with or without a tumour‐conditioned medium (TCM) derived from B16‐F10 melanoma. Obtained MDSCs were characterized by morphology, phenotype, gene expression of key immunosuppressive factors, and in vitro suppression of T cell proliferation. All tested protocols yielded approximately 25% monocytic and 50% polymorphonuclear MDSCs. Protocols using IL‐6 generated MDSCs with reduced maturation and differentiation status, upregulated Arg1 and Nos1 mRNA expression, increased levels of Arg‐1 and TGF‐β proteins and enhanced ROS production compared to the other protocols. All tested protocols yielded MDSCs that efficiently inhibited T cell proliferation in vitro, with some advantage for the GM‐CSF and G‐CSF + GM‐CSF protocols. Interestingly, a combination of protocols with B16‐F10‐derived TCM resulted in the generation of MDSCs with reduced immunosuppressive properties. Our results provide valuable insights into the optimal conditions for in vitro generation of MDSCs with specific immunosuppressive properties.

01 Feb 2025·Journal of Medical Virology

The Novel Oncolytic Herpes Simplex Virus Type‐1 (HSV‐1) Vaccine Strain VC2 Constitutively Expressing GM‐CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1/Balb/c Mouse Model of Stage Four Breast Cancer

Article

Author: Kousoulas, Konstantin G. ; Dutta, Ojasvi ; Davis, Megan E. ; Stanfield, Brent ; Ghavimi, Reza ; Mohan, Harikrishnan ; Chouljenko, Vladimir N. ; Musarrat, Farhana ; Nabi, Rafiq

ABSTRACTOncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type‐1 (HSV‐1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV‐1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) gene inserted in place of HSV‐1 Glycoprotein C (gC). We tested the efficacy of VC2‐GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM‐CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 104 plaque forming units (PFU) of VC2/VC2‐GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2‐GMCSF compared to VC2 or mock treatment. VC2‐GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2‐GMCSF treated animals, which was associated with reduced pro‐tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM‐CSF enhanced the overall efficacy of VC2 for OVT. VC2‐GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers.

01 Dec 2024·Advanced Science

Prolonged Survival of Neutrophils Induced by Tumor‐Derived G‐CSF/GM‐CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma

Article

Author: Ji, Yangyang ; Zhu, Xiaoke ; Lin, Hanqing ; Lu, Liming ; Zhang, Duo ; Ding, Xuping ; Zhou, Jian ; Tao, Lei ; He, Changding ; Ma, Jingyu ; Tang, Di ; Heng, Yu

AbstractTumor‐associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor‐derived G‐CSF and GM‐CSF through the activation of the PI3K‐AKT signaling pathway, upregulation of anti‐apoptotic Mcl‐1 expression, and downregulation of activated Caspase‐3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G‐CSF and GM‐CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.

100 Deals associated with GM-CSF(Sun Yat-sen University)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Nasopharyngeal Carcinoma	Phase 2	China	Sun Yat-Sen University	15 Sep 2023
Stomatitis	Phase 2	China	Sun Yat-Sen University	15 Sep 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SITC2015	Phase 2	Melanoma Adjuvant	62	GM-CSF (3 μg/kg)	llbullvrza(dilxmukdrw) = at a median follow-up of 79 months, this translated into a significantly longer recurrence-free survival (RFS) in the CpG-treated group (p=0.010) djvomvkkor (lhhvlqklrx )	Positive	04 Nov 2015
				CpG-B (PF-3512676/CpG7909, 8 mg)

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