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Related Concept Videos

Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
Adult stem cells
Adult stem cells are tissue-specific; hence, they divide to develop the tissue from which they originate. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of the skin. Adult bone marrow has three distinct types of stem cells:...
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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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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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Tumor Progression

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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
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CAR T cell persistence in cancer.

Katherine P Mueller1, Jeremy M Grenier1, Evan W Weber1

  • 1Department of Pediatrics, Division of Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Trends in Cancer
|September 19, 2025
PubMed
Summary

Chimeric antigen receptor T cell (CAR T) therapies show promise but struggle with poor cell persistence, limiting effectiveness against cancers. This review explores factors affecting CAR T persistence and strategies to improve these living drugs for better cancer treatment.

Keywords:
CAR TT cell exhaustioncancerimmunotherapypersistence

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Area of Science:

  • Immunotherapy
  • Cellular Therapy
  • Oncology

Background:

  • Chimeric antigen receptor T cell (CAR T) therapies are genetically engineered immune cells designed to target and eliminate cancer.
  • Poor in vivo persistence of CAR T cells is a significant challenge, hindering therapeutic efficacy in both liquid and solid tumors.

Purpose of the Study:

  • To review the current understanding of CAR T cell persistence in cancer treatment.
  • To explore factors influencing CAR T cell persistence, including clinical data, patient correlatives, and multiomics.
  • To discuss emerging strategies in cell engineering and manufacturing to enhance CAR T persistence and efficacy.

Main Methods:

  • Review of clinical observations and patient correlative studies.
  • Analysis of multiomics data to understand CAR T cell behavior.
  • Examination of novel cell engineering and manufacturing techniques.

Main Results:

  • Identified key factors contributing to limited CAR T cell persistence in patients.
  • Highlighted the role of multiomics in deciphering mechanisms of CAR T cell failure.
  • Showcased advancements in CAR T cell design and production.

Conclusions:

  • Improving CAR T cell persistence is crucial for enhancing therapeutic outcomes in cancer.
  • A conceptual framework is proposed to guide future research and clinical development of CAR T therapies.
  • Future strategies should focus on engineering more robust and long-lasting CAR T cells for improved cancer treatment.