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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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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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Related Experiment Video

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Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
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Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors.

Gang Xin1, David M Schauder1,2, Weiqing Jing3

  • 1Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213.

Proceedings of the National Academy of Sciences of the United States of America
|January 11, 2017
PubMed
Summary

This study introduces a novel cancer therapy combining adoptive cell transfer (ACT) with a pathogen vaccine. Engineered T cells and bacterial injection effectively eliminate solid tumors and establish long-term immunity.

Keywords:
CD8 T cellsListeriaadoptive cell transferimmunotherapymelanoma

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Area of Science:

  • Immunology
  • Oncology
  • Microbiology

Background:

  • Adoptive cell transfer (ACT) efficacy is limited in solid tumors due to poor T cell migration and the immunosuppressive tumor microenvironment (TME).
  • Overcoming these barriers is crucial for improving cancer immunotherapy outcomes.

Purpose of the Study:

  • To reenergize ACT (ReACT) by combining it with a pathogen-based cancer vaccine for enhanced solid tumor treatment.
  • To engineer dual-specific T cells capable of targeting both tumor and bacterial antigens.

Main Methods:

  • Genetically engineered tumor-specific CD8 T cells with a second T-cell receptor (TCR) recognizing a bacterial antigen in vitro.
  • Administered these dual-specific T cells combined with intratumoral bacteria injection in mouse models of solid tumors.

Main Results:

  • Dual-specific CD8 T cells showed vigorous expansion and migration to tumor sites.
  • The ReACT approach led to robust eradication of primary tumors and development of immunological memory against tumor rechallenge.
  • Mechanistically, the treatment reverted the immunosuppressive TME and increased the number and killing ability of CD8 T cells within tumors.

Conclusions:

  • The ReACT strategy effectively overcomes TME-induced suppression and enhances T cell-mediated antitumor immunity.
  • This combined immunotherapy approach shows significant promise for treating solid tumors.