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Engineered T cells and macrophages: two arms to seize solid tumors

Luigi Russo1, Ilaria De Martino1, Matteo Marchetti1

  • 1Istituto Italiano di Tecnologia - IIT, Largo Barsanti e Matteucci 53, Naples, Italy.

Current Opinion in Biotechnology
|March 27, 2025
PubMed

Insights

Genetically modified immune cells, like CAR T-cells, show promise for treating blood cancers. Engineering new functions and combining cell types may overcome challenges for solid tumor immunotherapy.

Area of Science:

  • Immunology
  • Biotechnology
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) T-cell therapy has shown success in hematological malignancies.
  • Significant barriers hinder CAR T-cell efficacy against solid tumors, necessitating enhanced functionalities for safety, migration, and persistence.
  • Macrophages offer complementary antitumor properties, including phagocytosis and antigen presentation, for a broader immune response.

Purpose of the Study:

  • To provide a comprehensive overview of current cell-based immunotherapy technologies.
  • To propose synthetic interplay between immune cells as a future breakthrough for improved cancer treatment.
  • To highlight strategies for overcoming solid tumor immunotherapy challenges.

Main Methods:

  • Review of recent advancements in genetically modified immune cell therapies.
  • Analysis of strategies for engineering immune cells, including T cells and macrophages.
  • Exploration of synthetic biology approaches for cell-cell communication in immunotherapy.

Main Results:

  • CAR T-cell therapy faces challenges in solid tumors, requiring additional engineered functions.
  • Macrophages possess properties that can augment antitumor immune responses.
  • Current research focuses on enhancing immune cell capabilities for broader therapeutic applications.

Conclusions:

  • Engineering synthetic interplay between different immune cells is a promising next step in cell-based immunotherapy.
  • This approach aims to develop safer and more effective living therapeutics for cancer treatment.
  • Overcoming solid tumor barriers requires innovative strategies beyond traditional CAR T-cell therapy.

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