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Related Concept Videos

Tumor Immunotherapy01:27

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.
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
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CD8+ T-cell responses against hemoglobin-beta prevent solid tumor growth.

Hideo Komita1, Xi Zhao, Jennifer L Taylor

  • 1Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.

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|October 3, 2008
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Engineered dendritic cells inhibited sarcoma growth. Vaccination with hemoglobin-beta peptides also protected against tumors by targeting vascular pericytes, with no adverse effects.

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Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • Dendritic cell (DC) therapy shows promise in cancer treatment.
  • Identifying tumor-specific antigens is crucial for effective cancer vaccines.
  • Tumor vasculature presents a potential target for anti-cancer therapies.

Purpose of the Study:

  • To investigate the anti-tumorigenic effects of IL-12p70-secreting dendritic cells.
  • To identify tumor antigens recognized by T cells in regressor mice.
  • To evaluate the therapeutic potential of hemoglobin-beta (HBB) peptide vaccination.

Main Methods:

  • Engineering bone marrow-derived dendritic cells with recombinant adenovirus to secrete IL-12p70.
  • Intratumoral administration of engineered DCs in CMS4 sarcoma-bearing mice.
  • Analysis of splenic CD8(+) T cell responses using HPLC-resolved peptides and mass spectrometry.
  • Reverse transcription-PCR to assess HBB mRNA expression in tumor cells.
  • Prophylactic vaccination with HBB peptides and subsequent tumor challenge.
  • In situ imaging of tumor vasculature and assessment of red blood cell parameters.

Main Results:

  • Engineered DCs significantly inhibited established CMS4 sarcoma growth.
  • CMS4 lesions yielded HBB-derived peptides that elicited strong CD8(+) T cell responses.
  • CMS4 tumor cells did not express HBB mRNA, suggesting HBB is a non-mutated tumor-associated antigen.
  • HBB peptide vaccination induced protective immunity against CMS4 and other syngeneic tumors.
  • Vaccination appeared to destabilize tumor vasculature, potentially via anti-HBB pericyte immunity.
  • HBB peptide vaccination did not adversely affect red blood cell parameters or vascular structures in the brain or eye.

Conclusions:

  • IL-12p70-secreting DCs are effective against established sarcomas.
  • HBB peptides can serve as targets for cancer vaccines, inducing protective immunity.
  • HBB-based vaccination may act by targeting tumor vasculature and associated pericytes.
  • HBB peptide vaccination is safe and does not impact normal red blood cell function or vital vascular structures.