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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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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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.
There are several types of targeted therapies against...
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Treatment Resistant Cancers02:56

Treatment Resistant Cancers

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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Related Experiment Video

Updated: Sep 9, 2025

Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy
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Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy

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Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

Julia Gwadera1, Maksymilian Grajewski1, Hanna Chowaniec2

  • 1Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

Biology
|September 4, 2025
PubMed
Summary

Engineered chimeric antigen receptor (CAR)-T cells show promise in overcoming solid tumor challenges. Strategies like metabolic reprogramming and combination therapies aim to enhance CAR-T cell efficacy against immunosuppressive tumor microenvironments.

Keywords:
CAR-T cellsCAR-T-cell therapyimmunosuppressionsolid tumourstumour microenvironment

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Area of Science:

  • Immunology
  • Synthetic Biology
  • Oncology

Background:

  • Chimeric antigen receptor (CAR)-T-cell therapy has transformed hematological cancer treatment.
  • Solid tumor treatment with CAR-T cells is hindered by the immunosuppressive tumor microenvironment (TME), poor antigen specificity, and infiltration barriers.

Purpose of the Study:

  • To explore the potential of adapting CAR-T cells to overcome solid tumor immunosuppression.
  • To analyze TME-related challenges and evaluate engineering strategies for enhanced CAR-T cell function.

Main Methods:

  • Review of immunological, metabolic, and structural TME challenges.
  • Evaluation of engineering strategies: metabolic reprogramming, hypoxia-responsive constructs, checkpoint resistance, and novel delivery systems.
  • Analysis of synergistic combination therapies (e.g., with immune checkpoint inhibitors, radiotherapy, oncolytic viruses).

Main Results:

  • Engineered "armored" CAR-T cells secreting cytokines (e.g., IL-12, IL-18) can reprogram the TME and restore anti-tumor immunity.
  • Preclinical and early clinical studies show promise for enhanced CAR-T cell persistence and function.
  • Personalized strategies like bispecific targeting and precision delivery demonstrate potential in overcoming resistance.

Conclusions:

  • CAR-T cell therapy holds significant potential for treating solid tumors by overcoming TME-induced immunosuppression.
  • Advancements in synthetic immunology offer hope for durable remissions and new treatment paradigms.
  • This review provides a roadmap for translating CAR-T cell therapy for solid tumors into clinical reality.