Breaking Bottlenecks for the TCR Therapy of Cancer
Abstract
:1. Immuno-Oncology’s Next Wave
2. The Unique Potential of T-Cell-Receptor (TCR) Therapy
3. Critical Tasks
3.1. Neoantigen Multitargeting
3.2. Next-Generation Products
3.2.1. T-Cell Persistence, Memory, and Fitness
3.2.2. Navigating and Prevailing in the TME
3.2.3. Avoiding Toxicity
4. Status of Clinical Development
5. Conclusions and Perspectives
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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CAR | TCR | |
---|---|---|
Target Ag | Surface proteins, glycoproteins, glycolipids, carbohydrates | Peptides from surface and intracellular proteins |
Ag recognition | MHC-independent | MHC-dependent |
Receptor structure | Single-chain, scFv 3 ITAMs | αβ heterodimer 10 ITAMs |
Affinity for target | Nanomolar range | Micromolar range |
Required target density for response | >103/cell | ∼1–50/cell |
Type of Antigen | Number of Trials | % of Active Trials 1 | % of Completed Trials | Start Year of the First Trial |
---|---|---|---|---|
Cancer-testis antigens (CTA) | 50 | 56% (28/50) | 12% (6/50) | 2008 |
Other tumor-associated antigens (TAA) | 25 | 44% (11/25) | 28% (7/25) | 2004 |
Oncoviral antigens | 17 | 88% (15/17) | 12% (2/17) | 2014 |
Neoantigens (public or private) | 12 | 75% (9/12) | 8% (1/12) | 2006 (public) 2018 (private) |
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Gaissmaier, L.; Elshiaty, M.; Christopoulos, P. Breaking Bottlenecks for the TCR Therapy of Cancer. Cells 2020, 9, 2095. https://doi.org/10.3390/cells9092095
Gaissmaier L, Elshiaty M, Christopoulos P. Breaking Bottlenecks for the TCR Therapy of Cancer. Cells. 2020; 9(9):2095. https://doi.org/10.3390/cells9092095
Chicago/Turabian StyleGaissmaier, Lena, Mariam Elshiaty, and Petros Christopoulos. 2020. "Breaking Bottlenecks for the TCR Therapy of Cancer" Cells 9, no. 9: 2095. https://doi.org/10.3390/cells9092095