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Tumor Immunotherapy

Tumor Immunotherapy

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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Challenges and solutions for therapeutic TCR-based agents.

Manish Malviya¹, Zita E H Aretz^1,2, Zaki Molvi^1,2

¹Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.

Immunological Reviews

|July 16, 2023

Summary

Therapeutic T-cell receptors (TCRs) offer new cancer treatments by targeting intracellular proteins. Overcoming challenges in discovery and specificity is key to realizing their full potential.

Keywords:

CAR T cells HLA restriction TCR gene therapy TCR-mimic mAb off-target toxicity soluble TCR

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Area of Science:

Immunology
Pharmacology
Oncology

Background:

Therapeutic antibodies have advanced significantly, but T-cell receptor (TCR)-based agents are emerging as a promising new class of therapeutics.
TCR-based therapies, including engineered cells and soluble TCRs, aim to target intracellular antigens inaccessible to traditional antibodies.

Purpose of the Study:

To review the opportunities and challenges associated with TCR-based therapeutic agents.
To compare TCR-based agents with traditional antibody therapeutics and CAR T cells.
To discuss the unique antigenic targets and hurdles for TCR-based drug development.

Main Methods:

Review of recent advancements in TCR discovery and engineering.
Analysis of the immunology and pharmacology of TCR-based agents.
Comparison of different TCR-based modalities (engineered cells, soluble TCRs, TCR-mimic antibodies, TCR-based CAR T cells).

Main Results:

TCR-based agents offer potential for highly specific drugs targeting intracellular mutated proteins and transcription factors.
Significant hurdles remain in TCR discovery, specificity, pharmacokinetics, and optimal modality of use.
HLA restriction and off-target reactivities are key barriers limiting patient subpopulations and widespread development.

Conclusions:

TCR-based agents represent a significant advancement in immunologic therapies, particularly for cancer treatment.
Further research and development are necessary to overcome existing obstacles for clinical application.
TCR-based therapies hold promise for expanding the scope of treatable conditions by targeting previously inaccessible antigens.