Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy
Abstract
:1. Introduction
2. Traditional Immunotherapeutic Modalities for the Treatment of Metastatic Melanoma
3. New Treatment Modalities: Targeted Therapies
3.1. Programmed Cell Death-1/Programmed Cell Death-Ligand 1 (PD-1/PD-L1) Immune Checkpoint Blockade
3.2. Cytotoxic T-Lymphocyte-Associated Protein (CTLA-4, CD152) Immune Checkpoint Blockade
4. Combination of Immune Checkpoint Inhibitors for the Treatment of Metastatic Melanoma Patients: Summary of Clinical Data
5. Targeted Therapy of Aberrant Signaling Molecules for the Treatment of Metastatic Melanoma Patients
6. Treatment of Metastatic Melanoma Patients Harboring BRAFV600E: A Summary of the Clinical Data
7. Recent T Cell-Based Immune Therapies for the Treatment of Metastatic Melanoma Patients
7.1. Molecular Basis for Using TCR-Engineered T Cells
7.2. Clinical Trials Involving TCR Immunotherapy: Molecular Aspects
7.3. Molecular Analysis of the Failure of TCR-Engineered T Cell Therapy: Adverse Effects
7.3.1. Cytokine Release Syndrome (CRS)
7.3.2. Autoimmune Responses
8. Molecular Mechanism of Resistance to TCR-transgenic T-Cell Adoptive Cell Transfer Immunotherapy
8.1. Primary Resistance to Immunotherapy
8.1.1. Defects in the Major Histocompatibility Complex (MHC)
8.1.2. Aberrant PI3K/AKT(PKB) Signaling Pathway and Loss of Phosphatase and Tensin Homolog Gene (PTEN)
8.1.3. Mutations in the Janus Kinase (JAK1/2) Signaling Module
8.2. Adaptive (Inherent/Primary)/Acquired (Secondary) Resistance to Immunotherapy
8.2.1. Treatment-Induced Hyperprogression and Potentiation of Tumor Cell Resistance to Immunotherapy
8.2.2. Role of T-Cell Immunoglobulin Mucin 3 (TIM-3)
8.2.3. Role of Apoptosis Machinery in Melanoma Resistance to T Cell-Based Therapies
9. Potential Mechanisms for Reversing TCR Immunotherapy Resistance
9.1. Paired ICI Treatments (PD-1 Paired with CTLA-4)
9.2. Biomarker Discovery
9.3. Chimeric Antigen Receptor (CAR) T Cell-Based Immunotherapy for Metastatic Melanoma
10. Discussion
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Jazirehi, A.R. Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy. Int. J. Mol. Sci. 2021, 22, 11726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111726
Jazirehi AR. Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy. International Journal of Molecular Sciences. 2021; 22(21):11726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111726
Chicago/Turabian StyleJazirehi, Ali R. 2021. "Molecular Analysis of Elements of Melanoma Insensitivity to TCR-Engineered Adoptive Cell Therapy" International Journal of Molecular Sciences 22, no. 21: 11726. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111726