Immune cell-based therapies for solid tumors, current challenges and therapeutic advances

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Solid tumors present significant therapeutic challenges due to antigen heterogeneity, physical barriers, and immunosuppressive tumor microenvironments (TME).
• Cancer immunotherapy has seen considerable advancements over the last decade, introducing novel strategies to combat these challenges.

Purpose of the Study:

• To summarize current immune cell-based therapies for solid tumors.
• To analyze their interaction with the TME, highlight clinical progress, and discuss bioengineering strategies to overcome resistance.
• To review cell-free extracellular vesicle (EV)-based approaches and future directions.

Main Methods:

• Review of existing literature on various immunotherapeutic modalities including CAR-T cells, dendritic-cell (DC) vaccines, and natural killer (NK) cells.
• Analysis of bioengineering strategies such as multi-antigen targeting, cytokine armoring, and safety switches.
• Evaluation of cell-derived extracellular vesicles (EVs) as a cell-free therapeutic option.

Main Results:

• Various modalities like CAR-macrophages, DC vaccines, NK/NKT cells, TIL therapy, TCR-engineered T cells, B-cell engineering, and EVs interact differently with the TME.
• Key clinical milestones include the FDA approval of a TIL product for melanoma in 2024.
• Bioengineering strategies aim to enhance efficacy and safety, while EV-based strategies offer potential advantages in safety and manufacturability.

Conclusions:

• Immune cell-based therapies are a rapidly maturing and transformative approach for treating solid tumors.
• Addressing challenges like manufacturing standardization, on-target/off-tumor effects, and limited persistence is crucial.
• Rational combinations with checkpoint blockade, radiotherapy, and targeted agents hold significant therapeutic potential.