Difference between revisions of "Part:BBa K5310010:Design"
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The sequence was retrieved from the NCBI database, the domain's use was evaluated in the literature, and the sequence was codon optimized for expression in human primary cell lines. | The sequence was retrieved from the NCBI database, the domain's use was evaluated in the literature, and the sequence was codon optimized for expression in human primary cell lines. | ||
| + | It has been demonstrated in literature that the main activation domain benefits from the existence of co-stimulatory sequences that amplify signaling and prolong CAR T-cell survival. While this started with a single co-stimulatory endodomain (2nd generation), it was quickly established that a combination (3rd generation) produces better results. The domains used almost exclusively are CD28 (encoded by BBa_K5310009) and 4-1BB (encoded by BBa_K5310010). | ||
| − | + | 4-1BB belongs to the TNF receptor family and promotes T-cell proliferation via a pathway called ncNF-κB (non-canonical nuclear factor κB). Upon ligand-induced trimerization of 4-1BB, TNF receptor–associated factors (TRAF) are recruited, shifting ubiquitination from NIK to TRAF3. NIK, which is normally ubiquitinated and degraded, can now accumulate and trigger a signaling cascade that ends with the activation of important lymphocyte development genes. | |
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===Source=== | ===Source=== | ||
Revision as of 09:44, 30 September 2024
CD137 signalling domain
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Design Notes
The sequence was retrieved from the NCBI database, the domain's use was evaluated in the literature, and the sequence was codon optimized for expression in human primary cell lines.
It has been demonstrated in literature that the main activation domain benefits from the existence of co-stimulatory sequences that amplify signaling and prolong CAR T-cell survival. While this started with a single co-stimulatory endodomain (2nd generation), it was quickly established that a combination (3rd generation) produces better results. The domains used almost exclusively are CD28 (encoded by BBa_K5310009) and 4-1BB (encoded by BBa_K5310010).
4-1BB belongs to the TNF receptor family and promotes T-cell proliferation via a pathway called ncNF-κB (non-canonical nuclear factor κB). Upon ligand-induced trimerization of 4-1BB, TNF receptor–associated factors (TRAF) are recruited, shifting ubiquitination from NIK to TRAF3. NIK, which is normally ubiquitinated and degraded, can now accumulate and trigger a signaling cascade that ends with the activation of important lymphocyte development genes.
Source
The 4-1-BB signalling domain sequence was retrieved from the CD28 gene that resides on chromosome 2 of the human genome.