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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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Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo.

Brittany L Bunch1, Jennifer Morse1, Sarah Asby1

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Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) shows promise for bladder cancer treatment. Intravesical TIL therapy effectively controlled tumor growth in mice, offering a new therapeutic avenue.

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Area of Science:

  • Oncology
  • Immunology
  • Cell Therapy

Background:

  • Bladder cancer therapies, including immune checkpoint inhibitors and antibody drug conjugates, show limited response duration.
  • Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) presents a potential treatment strategy for bladder cancer.
  • Successful expansion of tumor-reactive T cells from human bladder tumors supports TIL therapy's potential.

Purpose of the Study:

  • To investigate the efficacy of ACT with TILs in a preclinical bladder cancer model.
  • To compare systemic versus intravesical delivery of TILs for bladder cancer treatment.
  • To elucidate the role of CXCR3 in TIL-mediated anti-tumor responses.

Main Methods:

  • Developed a model using OT-I T cells and MB49OVA tumor cells for ACT studies.
  • Administered systemic ACT intravenously post-chemotherapy with IL-2, and intravesical ACT directly into the bladder without chemotherapy or IL-2.
  • Isolated and expanded TILs from MB49 tumors ex vivo, analyzed immune infiltrates via flow cytometry, and blocked CXCR3 to study T cell infiltration.

Main Results:

  • Systemic ACT reduced tumor growth, increased T cell infiltration, and provided long-term immunity.
  • Intravesical ACT controlled tumor growth in MB49OVA tumors without chemotherapy or IL-2.
  • Intravesical delivery of expanded TILs also decreased tumor growth in MB49 tumors.
  • Blocking CXCR3 on T cells reduced tumor infiltration and impaired tumor growth control.

Conclusions:

  • TIL therapy demonstrates potential for treating various stages of bladder cancer.
  • Intravesical delivery of TILs is an effective strategy for bladder cancer treatment.
  • CXCR3 plays a crucial role in TIL trafficking and anti-tumor efficacy.