Antitumor Activity of Liposomal Prednisolone Phosphate Depends on the Presence of Functional Tumor-Associated Macrophages in Tumor Tissue

The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis. In this review, we will discuss the potential implication of HCMV in breast cancer with emphasis on the role played by macrophages.

Download Full-text

Tumor-Associated Macrophages Can Contribute to Antitumor Activity through FcγR-Mediated Processing of Antibody–Drug Conjugates

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-17-0019 ◽

2017 ◽

Vol 16 (7) ◽

pp. 1347-1354 ◽

Cited By ~ 25

Author(s):

Fu Li ◽

Michelle Ulrich ◽

Mechthild Jonas ◽

Ivan J. Stone ◽

Germein Linares ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Associated Macrophages ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Antibody Drug

Download Full-text

ACONITINE-CONTAINING AGENT ENHANCES ANTITUMOR ACTIVITY OF DICHLOROACETATE AGAINST EHRLICH CARCINOMA

Experimental Oncology ◽

10.31768/2312-8852.2015.37(3):192-196 ◽

2015 ◽

Vol 37 (3) ◽

pp. 192-196 ◽

Cited By ~ 3

Author(s):

O N Pyaskovskaya ◽

I V Boychuk ◽

A G Fedorchuk ◽

D L Kolesnik ◽

O I Dasyukevich ◽

...

Keyword(s):

Antitumor Activity ◽

Total Dose ◽

Lactate Level ◽

Phagocytic Activity ◽

Tumor Tissue ◽

Antitumor Action ◽

Ehrlich Carcinoma ◽

Ros Production ◽

Antiangiogenic Agent ◽

Ldh Activity

Significant variability of anticancer efficacy of dichloroacetate (DCA) stimulated an active search for the agents capable to enhance it antitumor action. Therefore, the aim of this work is the study of capability of aconitine-containing antiangiogenic agent BC1 to enhance anticancer activity of DCA against Ehrlich carcinoma. Materials and Methods: DCA (total dose was 1.3 g/kg of b.w.) and BC1 (total dose was 0.9 mg/kg of b.w.) were administered per os starting from the 2nd and 3rd days, respectively (8 admini strations for each agent). Antitumor efficacy of agents was estimated. Lactate level, LDH activity and the state of mitochondrial electron transport chain in tumor cells as well as phagocytic activity and reactive oxygen species (ROS) production of tumor-associated macrophages (TAM) were studied. Results: Combined administration of DCA and ВС1 resulted in 89.8% tumor growth inhibition (p < 0.001), what is by 22.5% (p < 0.05) higher that that of DCA alone. This combined treatment was accompanied with a decrease of lactate level in tumor tissue by 30% (p < 0.05) and significant elevation of LDH activity by 70% (p < 0.01). Increased level of NO-Fe-S clusters and 2-fold reduction of Fe-S cluster content were revealed in tumor tissue of mice after DCA and BC1 administration. It was shown that combined therapy did not effect TAM quantity and their phagocytic activity but stimulated ROS production by TAMs by 78% (p < 0.05) compared to this index in control animals. Conclusion: Antiangiogenic agent ВС1 in combination with DCA considerably enhances antitumor activity of DCA via significant decrease of Fe-S-containing protein level resulted from substantial elevation of nitrosylation of these proteins.

Download Full-text

Abstract 1285: Tumor associated macrophages can process antibody-drug conjugates and contribute to antitumor activity in preclinical xenograft models

10.1158/1538-7445.am2016-1285 ◽

2016 ◽

Cited By ~ 1

Author(s):

Fu Li ◽

Michelle Ulrich ◽

Mechthild Jonas ◽

Germein Linares ◽

Xinqun Zhang ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Associated Macrophages ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Xenograft Models ◽

Antibody Drug

Download Full-text

Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model

Cell Communication and Signaling ◽

10.1186/s12964-020-00570-5 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Benfan Wang ◽

Qinyan Li ◽

Jinyan Wang ◽

Siting Zhao ◽

Bayaer Nashun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Tumor Angiogenesis ◽

Tumor Tissue ◽

Tumor Resection ◽

Mapk Signaling ◽

Mechanistic Study ◽

High Recurrence Rate ◽

Tumor Associated Macrophages ◽

Hepatoma Model

Abstract Background Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of an effective treatment for this disease results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate of these patients remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model. Methods This study aimed to investigate the inhibitory effect of Plasmodium infection on hepatocellular carcinoma in mice, and various techniques for gene expression analysis were used to identify possible signal regulation mechanisms. Results We found that Plasmodium infection efficiently inhibited tumor progression and prolonged survival in tumor-bearing mice, which served as a murine implanted hepatoma model. The inhibition of tumor progression by Plasmodium infection was related to suppression of tumor angiogenesis within the tumor tissue and decreased infiltration of tumor-associated macrophages (TAMs). Further study demonstrated that matrix metalloprotease 9 (MMP-9) produced by TAMs contributed to tumor angiogenesis in the tumor tissue and that the parasite-induced reduction in MMP-9 expression in TAMs resulted in the suppression of tumor angiogenesis. A mechanistic study revealed that the Plasmodium-derived hemozoin (HZ) that accumulated in TAMs inhibited IGF-1 signaling through the PI3-K and MAPK signaling pathways and thereby decreased the expression of MMP-9 in TAMs. Conclusions Our study suggests that this novel approach of inhibiting tumor angiogenesis by Plasmodium infection is of high importance for the development of new therapies for cancer patients.

Download Full-text

EVALUATION OF ANTITUMOR ACTIVITY OF TUMOR NECROSIS FACTOR ALPHA WITHIN THE ARTIFICIAL VIRUS-LIKE PARTICLE

Russian Journal of Biotherapy ◽

10.17650/1726-9784-2019-19-1-96-103 ◽

2020 ◽

Vol 19 (1) ◽

pp. 96-103 ◽

Cited By ~ 1

Author(s):

G. M. Sysoeva ◽

E. I. Ryabchikova ◽

O. V. Simakova ◽

E. A. Volosnikova ◽

L. R. Lebedev ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Antitumor Activity ◽

Tumor Growth ◽

Delivery System ◽

Tumor Necrosis ◽

Tumor Tissue ◽

Virus Like Particle ◽

Artificial Virus ◽

Tnf Α ◽

Necrosis Factor

Introduction. Tumor necrosis factor α (TNF-α) is a natural cytokine, characterized by pronounced antitumor properties. A wide range of side effects serves as an obstacle for the use of TNF-α in clinical practice. One of the ways to improve its therapeutic properties is to increase the tropism of the cytokine to the tumor tissue by incorporating it into the targeted delivery system.The aim of the study was to evaluate the antitumor activity of the preparation containing TNF-α as part of the artificial “virus-like particle” (VLP-TNF-α), developed in SRC VB “Vector” as a transport system for delivering proteins to target cells.Materials and methods. The antitumor effect of VLP-TNF-α preparation was evaluated in experimental B16F10 melanoma model by the change of dynamics of tumor growth (volume, mass) and its morphological structure (presence of necrotic processes, blood vessel destruction). The number of the effector immune cells (CD3+, CD11b+) in the tumor tissue was determined by immunohistochemical method.Results. It has been shown that VLP-TNF-α administered intravenously at the doses of 5 × 104 and 1 × 105 IU/mouse inhibits the growth of the primary tumor. The most pronounced and stable effect was observed with a five-fold administration at the dose of 1 × 105 IU/mouse every other day: tumor growth inhibition was 40 % on the 1st day, and 47 % on the 7 th day upon the treatment. Injections of the preparation resulted in the increase of necrosis number, destruction level of the tumor tissue, development of damage and destruction of the tumor blood vessels and its infiltration with immunocompetent cells.Conclusion. The obtained data indicates that TNF-α within the delivery system exerts antitumor activity, which suggests the possibility of its further use for the treatment of malignant neoplasms, in particular, melanoma.The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.

Download Full-text

Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model

10.21203/rs.2.17456/v1 ◽

2019 ◽

Author(s):

Benfan Wang ◽

Qinyan Li ◽

Jinyan Wang ◽

Siting Zhao ◽

Bayaer Nashun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Tumor Angiogenesis ◽

Tumor Tissue ◽

Tumor Resection ◽

Mapk Signaling ◽

Mechanistic Study ◽

Plasmodium Infection ◽

Tumor Associated Macrophages ◽

Hepatoma Model

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in China. The lack of effective treatment results in a high recurrence rate in patients who undergo radical tumor resection, and the 5-year survival rate remains low. Our previous studies demonstrated that Plasmodium infection provides a potent antitumor effect by inducing innate and adaptive immunity in a murine Lewis lung carcinoma (LLC) model. Methods: A study was conducted to investigate the inhibitory effect of Plasmodium infection on hepatocellular carcinoma in mice, and chip analysis techniques were used to find possible signal regulation mechanisms. Results: we report that Plasmodium infection efficiently inhibited tumor progression and prolonged survival in tumor-bearing mice in a murine implanted hepatoma model. The inhibition of tumor progression by Plasmodium infection is related to the suppression of tumor angiogenesis within the tumor tissue and the decreased infiltration of tumor-associated macrophages (TAMs). Further study demonstrated that TAM-produced matrix metalloprotease 9 (MMP-9) contributed to tumor angiogenesis in the tumor tissue and that the reduced expression of MMP-9 in TAMs mediated by parasite infection resulted in the suppression of tumor angiogenesis. A mechanistic study revealed that the Plasmodium-derived hemozoin (HZ) that accumulated in TAMs inhibited IGF-1 signaling through the PI3-K and MAPK signaling pathways, which led to decreased expression of MMP-9 in TAMs. Conclusions: Our study suggests that this novel method of inhibiting tumor angiogenesis by Plasmodium infection is of high importance for developing new therapies for cancer patients.

Download Full-text

Vα24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages

Journal of Clinical Investigation ◽

10.1172/jci37869 ◽

2009 ◽

Vol 119 (6) ◽

pp. 1524-1536 ◽

Cited By ~ 176

Author(s):

Liping Song ◽

Shahab Asgharzadeh ◽

Jill Salo ◽

Kelly Engell ◽

Hong-wei Wu ◽

...

Keyword(s):

Antitumor Activity ◽

Nkt Cells ◽

Tumor Associated Macrophages ◽

Invariant Nkt Cells

Download Full-text

CTNI-16. TROTABRESIB (CC-90010, BMS-986378), A REVERSIBLE, POTENT ORAL BROMODOMAIN AND EXTRATERMINAL INHIBITOR (BETi) IN PATIENTS WITH HIGH-GRADE GLIOMAS: A PHASE 1 OPEN-LABEL ‘WINDOW OF OPPORTUNITY’ STUDY

Neuro-Oncology ◽

10.1093/neuonc/noab196.241 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi62-vi62

Author(s):

Michael Vogelbaum ◽

Juan Manuel Sepulveda ◽

David Reardon ◽

Bishoy Hanna ◽

Ellen Filvaroff ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Tissue ◽

Tissue Concentration ◽

Phase 1 ◽

Geometric Mean ◽

Study Drug ◽

Recurrent Glioblastoma ◽

Percentage Increase ◽

Open Label ◽

Salvage Resection

Abstract Trotabresib is a potent, reversible oral BETi with antitumor activity in patients with advanced malignancies (Moreno et al. ESMO 2020. Abstract 5270). The CC-90010-GBM-001 study (NCT04047303) enrolled patients with progressive or recurrent astrocytoma or recurrent glioblastoma scheduled for salvage resection. Patients were treated with trotabresib 30 mg daily for 4 days before surgery, then trotabresib 45 mg daily 4 days on/24 days off after recovery. Primary objectives were trotabresib tumor tissue concentration and plasma pharmacokinetics (PK). Secondary and exploratory objectives included safety, antitumor activity, cerebrospinal fluid concentration, and pharmacodynamics (PD). Twenty patients were enrolled; blood PK, blood PD, and tumor PD data were available for 14, 12, and 11 patients, respectively. Geometric mean peak trotabresib plasma concentration on day 4 was 1.92 μM; median time to peak concentration was 1.5 hours. At the time of resection, geometric mean trotabresib concentrations in plasma and brain tumor tissue were 1.01 and 0.68 μM, respectively. Blood CCR1 mRNA was reduced ≥ 50% from baseline after dose 4. Blood HEXIM1 mRNA increased at 72–96 hours following first dose, and at the time of surgery the percentage increase was related to plasma trotabresib concentration. Tumor HEXIM1 RNA increased in 10 of 11 patients. Eighteen patients (90%) had ≥ 1 treatment-related adverse event (TRAE). Nine patients (45%) had grade 3/4 TRAEs, most frequently thrombocytopenia (5 patients [25%]). Only 1 patient had serious TRAEs (hemiparesis and lethargy). Two patients died of intracranial hemorrhage unrelated to study drug. Of 16 patients evaluable for antitumor response, 7 had stable disease per RANO criteria, with 3 ongoing beyond data cutoff at cycles 4–11. Median progression-free survival was 1.9 months (95% CI, 1.4–3.3). Overall, trotabresib showed good tumor tissue penetration, with PD signals of response, and was well tolerated. A study of trotabresib + temozolomide in first-line glioblastoma is ongoing (NCT04324840).

Download Full-text