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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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Imaging CAR T-cell kinetics in solid tumors: Translational implications.

Matthew S Skovgard1, Hocine R Hocine1, Jasmeen K Saini1

  • 1Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Molecular Therapy Oncolytics
|September 23, 2021
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Summary

Chimeric antigen receptor (CAR) T-cell therapy for solid tumors faces challenges. New dual imaging methods reveal how T-cell delivery and tumor factors impact CAR T-cell behavior, guiding improved cancer treatments.

Keywords:
CAR T cellsPET-CTcell therapygene therapyimaging reporterimmunotherapyimmunotherapy kineticsin vivo imaginglung cancermesotheliomanoninvasive immunotherapy imaging

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Area of Science:

  • Immunotherapy
  • Oncology
  • Medical Imaging

Background:

  • Solid tumor chimeric antigen receptor (CAR) T-cell therapy faces significant barriers, including T-cell sequestration in the lungs, poor tumor infiltration, and heterogeneous antigen expression.
  • Accurate assessment of CAR T-cell kinetics is crucial for interpreting therapy response and limitations in solid tumors, but current methods like peripheral blood analysis or single-site biopsies are insufficient.
  • Tumor imaging alone has also proven inadequate for evaluating the efficacy of T-cell-based therapies.

Purpose of the Study:

  • To address the limitations in assessing CAR T-cell kinetics in solid tumors, this study aimed to develop and utilize dual tumor and T-cell imaging techniques.
  • To investigate the influence of T-cell delivery methods, activation status, and tumor antigen heterogeneity on CAR T-cell kinetics in relevant preclinical models.

Main Methods:

  • Employed dual tumor and T-cell imaging using a bioluminescent reporter and positron emission tomography (PET).
  • Utilized clinically relevant mouse models of pleural mesothelioma and non-small cell lung cancer.
  • Assessed CAR T-cell kinetics in relation to systemic versus regional delivery, tumor antigen expression, and T-cell activation status.

Main Results:

  • Observed that the mode of T-cell delivery (systemic vs. regional) significantly impacts T-cell kinetics.
  • Demonstrated that T-cell activation status, dependent on antigen-expressing tumors, influences T-cell accumulation and behavior.
  • Highlighted the role of tumor-antigen expression heterogeneity in modulating CAR T-cell kinetics within the tumor microenvironment.

Conclusions:

  • The study underscores the need for advanced imaging techniques to accurately track CAR T-cells in solid tumors.
  • Identified key factors influencing CAR T-cell kinetics, including delivery method and tumor characteristics.
  • Emphasizes the necessity of developing T-cell reporters for repeat *in vivo* imaging alongside standard tumor imaging and efficacy assessments to optimize CAR T-cell therapy for solid tumors.