Part:BBa_K5073029:Design
IL-12：Secretion of IL-12
- 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
In CAR-T therapy, several key factors need to be considered when designing the sequence of IL-12 to ensure its efficacy and safety in CAR-T cells. Firstly, the complete functional sequence of IL-12 must be preserved to ensure that the two subunits, p35 and p40, are able to fold correctly and form a functional dimer to exert biological activity. In addition, promoter selection needs to be optimized to ensure that IL-12 is expressed at the right amount in T cells to avoid adverse immune responses caused by over-activation. It is also crucial to assess the stability and biological activity of IL-12 in the tumor microenvironment to ensure that it can be efficiently released in the tumor environment and induce appropriate immune responses. In addition, the interaction of IL-12 with other CAR components, such as CD3ζ and co-stimulatory molecules, needs to be considered to ensure that they are coordinated in signaling to maximize the anti-tumor capacity of CAR-T cells. These design considerations will ensure the efficacy and safety of IL-12 in CAR-T cell therapy.
Source
In CAR-T therapy, the source of IL-12 is primarily the gene sequence.IL-12 consists of two subunits (p35 and p40), which are encoded by the IL12A and IL12B genes, located on human chromosome 3 (IL12A) and chromosome 5 (IL12B), respectively. In genetic engineering, researchers usually use the coding sequences of these genes to construct expression vectors for the production of IL-12 in CAR-T cells. By integrating the gene sequences of IL-12 into the CAR structure, it is possible to efficiently express IL-12 in transduced T-cells, thereby enhancing its anti-tumor activity.