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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...

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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

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Published on: January 6, 2014

Tumor Antigen-Primed Dendritic Cell-Derived Exosome Synergizes with Colony Stimulating Factor-1 Receptor Inhibitor by

Anjali Barnwal^1,2, Vidit Gaur^1,2, Anindita Sengupta^1,2

¹Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi 110016, India.

ACS Biomaterials Science & Engineering

|October 23, 2023

Summary

Maturing dendritic cell-derived exosomes (mDexTA) combined with a CSF-1R inhibitor (PLX-3397) effectively delayed tumor growth and improved survival in melanoma models by enhancing T cell infiltration and modulating the tumor microenvironment.

Keywords:

CSF-1R inhibitor Cancer immunotherapy DC-derived exosomes Melanoma PLX-3397 Tumor microenvironment

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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Area of Science:

Immunology
Cancer Therapy
Exosome Biology

Background:

Dendritic cell-derived exosomes (Dex) show promise but face challenges in clinical efficacy due to inadequate dendritic cell (DC) maturation and immunosuppressive tumor microenvironments (TME).
Targeting the CSF-1/CSF-1R pathway can deplete immunosuppressive cells like tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) within the TME.

Purpose of the Study:

To investigate the efficacy of mature Dex loaded with tumor antigen (mDexTA) in combination with a CSF-1R inhibitor (PLX-3397) for enhancing antitumor immunity.
To evaluate the impact of this combination therapy on immune cell infiltration, TME modulation, and overall survival in a preclinical melanoma model.

Main Methods:

Bone marrow-derived DCs were cultured with a maturation cocktail and tumor antigen to generate mDexTA.
PLX-3397, a CSF-1R inhibitor, was used in combination with mDexTA in the B16-F10 murine melanoma model.
Immune cell populations (CD8 T cells, TAMs, MDSCs, Th1/Th2) and tumor growth were analyzed.

Main Results:

mDexTA exhibited enhanced expression of MHCs and co-stimulatory molecules, activating naive DCs and T cells more effectively than immature Dex.
The combination of mDexTA and PLX-3397 significantly delayed tumor growth and improved survival compared to mDexTA monotherapy.
Combination treatment promoted CD8 T cell infiltration, shifted the Th1/Th2 balance towards Th1, and depleted TAMs and MDSCs in the TME.

Conclusions:

The combination of mDexTA and PLX-3397 demonstrates synergistic antitumor effects, overcoming limitations of monotherapy.
This combination therapy represents a promising strategy for treating solid tumors, including melanoma, by enhancing anti-tumor immunity and modulating the TME.