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Background <p>Chimeric antigen receptor (CAR) T&#xa0;cell treatment is based on the concept of specifically targeting the patient’s cytolytic T&#xa0;cells against tumors using a&#xa0;synthetic receptor signaling molecule (CAR).</p> Objective <p>While CAR T&#xa0;cells show unprecedented efficacy against hematological neoplasms, CAR T&#xa0;cell treatment of solid tumors has so far been largely disappointing, with causes still being only partially understood.</p> Method <p>Presentation of the dominant mechanisms that prevent CAR T&#xa0;cell activation in solid tumors and strategies to overcome these obstacles.</p> Results <p>Preclinical research on tumor models and clinical trials in recent years have shown that CAR T&#xa0;cell activation is effectively suppressed in many solid tumors by the prevention of T&#xa0;cell penetration into the tumor as well as active suppression of T&#xa0;cell functions and metabolic conditions that limit T&#xa0;cell survival within the tumor. To overcome these obstacles, various strategies are being tested experimentally and clinically, such as pretreatment of tumors, increasing T&#xa0;cell resistance to suppressive cytokines and metabolites as well as activation of resident immune cells by CAR-mediated release of therapeutically effective cytokines (T&#xa0;cells redirected for unrestricted cytokine-mediated killing, TRUCK).</p> Conclusion <p>There is considerable developmental potential to make CAR T&#xa0;cell treatment effective against solid tumors. Novel strategies that use CAR T&#xa0;cells as “biopharmaceutical factories” (TRUCK) to selectively activate natural killer (NK) cells and macrophages in tumor tissues recently entered the clinical trial stage.</p>

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CAR-T-Zellen bei soliden Tumoren – Mechanismen der Resistenz

  • 期刊论文

  • 发表日期：

    2025年6月25日

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  • Markus Barden,
  • Astrid Holzinger,
  • Hinrich Abken

摘要

Background

Chimeric antigen receptor (CAR) T cell treatment is based on the concept of specifically targeting the patient’s cytolytic T cells against tumors using a synthetic receptor signaling molecule (CAR).

Objective

While CAR T cells show unprecedented efficacy against hematological neoplasms, CAR T cell treatment of solid tumors has so far been largely disappointing, with causes still being only partially understood.

Method

Presentation of the dominant mechanisms that prevent CAR T cell activation in solid tumors and strategies to overcome these obstacles.

Results

Preclinical research on tumor models and clinical trials in recent years have shown that CAR T cell activation is effectively suppressed in many solid tumors by the prevention of T cell penetration into the tumor as well as active suppression of T cell functions and metabolic conditions that limit T cell survival within the tumor. To overcome these obstacles, various strategies are being tested experimentally and clinically, such as pretreatment of tumors, increasing T cell resistance to suppressive cytokines and metabolites as well as activation of resident immune cells by CAR-mediated release of therapeutically effective cytokines (T cells redirected for unrestricted cytokine-mediated killing, TRUCK).

Conclusion

There is considerable developmental potential to make CAR T cell treatment effective against solid tumors. Novel strategies that use CAR T cells as “biopharmaceutical factories” (TRUCK) to selectively activate natural killer (NK) cells and macrophages in tumor tissues recently entered the clinical trial stage.