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Updated: Jun 6, 2026
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy
Xinmei Zhu1, Mitsugu Fujita, Linda A Snyder
1Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Abstract:
Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) inhibit anti-tumor immune responses and facilitate tumor growth. Precursors for these immune cell populations migrate to the tumor site in response to tumor secretion of chemokines, such as monocyte chemoattractant protein-1 (MCP-1/CCL2), which was originally purified and identified from human gliomas. In syngeneic mouse GL261 glioma and human U87 glioma xenograft models, we evaluated the efficacy of systemic CCL2 blockade by monoclonal antibodies (mAb) targeting mouse and/or human CCL2. Intraperitoneal (i.p.) administration of anti-mouse CCL2 mAb as monotherapy (2 mg/kg/dose, twice a week) significantly, albeit modestly, prolonged the survival of C57BL/6 mice bearing intracranial GL261 glioma (P = 0.0033), which was concomitant with a decrease in TAMs and MDSCs in the tumor microenvironment. Similarly, survival was modestly prolonged in severe combined immunodeficiency mice bearing intracranial human U87 glioma xenografts treated with both anti-human CCL2 mAb and anti-mouse CCL2 antibodies (2 mg/kg/dose for each, twice a week) compared to mice treated with control IgG (P = 0.0159). Furthermore, i.p. administration of anti-mouse CCL2 antibody in combination with temozolomide (TMZ) significantly prolonged the survival of C57BL/6 mice bearing GL261 glioma with 8 of 10 treated mice surviving longer than 70 days, while only 3 of 10 mice treated with TMZ and isotype IgG survived longer than 70 days (P = 0.0359). These observations provide support for development of mAb-based CCL2 blockade strategies in combination with the current standard TMZ-based chemotherapy for treatment of malignant gliomas.
Insights
Blocking monocyte chemoattractant protein-1 (CCL2) with antibodies reduced immunosuppressive cells in gliomas. This strategy, combined with chemotherapy, improved survival in preclinical glioma models.
Area of Science:
- Immunology
- Oncology
- Neuroscience
Background:
- Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) promote tumor growth by suppressing anti-tumor immunity.
- Chemokines like monocyte chemoattractant protein-1 (CCL2), secreted by gliomas, attract TAM and MDSC precursors to the tumor microenvironment.
- CCL2 blockade is a potential therapeutic strategy for malignant gliomas.
Purpose of the Study:
- To evaluate the efficacy of systemic CCL2 blockade using monoclonal antibodies (mAbs) in preclinical glioma models.
- To assess the impact of CCL2 blockade on TAM and MDSC infiltration in the tumor microenvironment.
- To determine if CCL2 blockade enhances the efficacy of temozolomide (TMZ) chemotherapy in glioma treatment.
Main Methods:
- Utilized syngeneic GL261 glioma and human U87 glioma xenograft mouse models.
- Administered anti-mouse and/or anti-human CCL2 mAbs systemically via intraperitoneal injection.
- Evaluated survival rates and quantified TAM and MDSC populations within tumors.
- Assessed the combination therapy of anti-CCL2 mAb with temozolomide (TMZ).
Main Results:
- Systemic anti-CCL2 mAb monotherapy modestly prolonged survival in both GL261 and U87 glioma models.
- CCL2 blockade led to a decrease in TAMs and MDSCs within the tumor microenvironment.
- Combination therapy with anti-CCL2 mAb and TMZ significantly improved survival in GL261 glioma-bearing mice compared to TMZ alone.
Conclusions:
- Systemic CCL2 blockade is a promising strategy to reduce immunosuppressive myeloid cells in gliomas.
- Combining CCL2 blockade with standard TMZ chemotherapy may enhance treatment efficacy for malignant gliomas.
- Further clinical development of mAb-based CCL2 blockade for glioma treatment is warranted.
