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CAR-T cells can detect antigens and activate cytotoxic activity to destroy tumor cells, and their efficiency is closely related to the differences in T cell function. Less differentiated T cells, such as naïve T cells (Tn), T memory stem cells (Tscm), and central memory T cells (Tcm), exhibit higher anti-tumor efficacy than CAR-T cells produced from T effector memory cells (Tem) and effector T cells (Teff).
Using a mixture of cytokines, researchers have shown that diverse phenotypes of T cells may be generated. As a result, choosing optimal cytokines or a combination of cytokines to cultivate T cells is a viable technique for increasing CAR-T cell effectiveness.
When murine lymphocyte cells were cultivated and expanded in vitro in media containing IL-2 and IL-15, the findings revealed that T cells cultured with IL-2 primarily differentiated into T effector memory cells (Tem), whereas cells cultured with IL-15 primarily differentiated into central memory T cells (Tcm).
In terms of function, IL-15 encourages T cells to produce additional anti-tumor molecules, including IFN-γ, TNF-α, IL-10, IL-2, and so on.1
IL-15 prompts T cells to secrete more antitumor factors. Proc Natl Acad Sci U S A. 2004 Feb 17; 101(7): 1969–1974. Image Credit: ACROBiosystems
IL-7+15 has a greater expansion impact on CD19-CAR-CD8+ T cells than IL-2 and aids in the retention of CD45RA and CCR7 expression. The effector function, as well as the anti-tumor activity of CAR-T cells, is also enhanced upon antigen-specific stimulation, which is accompanied by a considerable rise in IFN-γ secretion.2
CAR-T cells cultured with IL7+15 have stronger antitumor activity Blood. 2014 Jun 12; 123(24): 3750–3759. Image Credit: ACROBiosystems
Researchers consistently found that CAR-T cells exposed to IL-2 had a short half-life and vanished by day 3 post-infusion in NSG mice engrafted with a high tumor load of Raji cells and infused with CAR-T cells.
In contrast, however, IL-7 and IL-15 expanded CAR-T cells were detectable for more than 14 days after infusion and appeared to accumulate in the spinal cord, where tumor cells were primarily localized. Mice that were given IL-7 and IL-15 expanded CAR-T cells had substantial delays in disease/paralysis development.
CAR-T cultured with IL-7+15 has long survival time and strong antitumor activity Blood. 2014 Jun 12; 123(24): 3750–3759. Image Credit: ACROBiosystems
CAIX CARs were expanded using IL2, IL7 + 15, or IL15 + 21 in a study. The results showed that T cells multiplied best with IL-15+21, which promoted the higher expansion of CD8 + T cells and could thus generate activated CAR-T kill-activity.
IL15+21 has the better effect of expansion T cells and enhance the ability of killing tumor Hum Gene Ther Methods. 2014 Dec 1; 25(6): 345–357. Image Credit: ACROBiosystems
Finally, cytokines like IL-7, IL-15, IL-21, and IL-2 are critical in the development of cell therapy. These cytokines are critical raw materials in cell therapy and have a tight relationship to clinical therapeutic impact. The FDA and the Chinese Pharmacopoeia have relevant regulations for the usage of these critical materials.
The FDA CMC advises that materials be FDA-approved or clinical-grade. Priority must be given to the use of low-risk materials, including pharmaceutical grade and GMP grade materials, over non-GMP grade materials per Chinese Pharmacopoeia rules.
Since most raw materials are not accessible in the pharmaceutical stage, GMP grade is the first option for many pharmaceutical companies. However, it is important to consider how to confirm that the raw material is indeed GMP grade.
ACROBiosystems is dedicated to the creation of high-quality reagents for use in immune cell therapy clinical trials. Researchers have successfully created a range of high-quality GMP-grade cytokines such as IL-15, IL-7, and IL-21 to assist the cell therapy development process, based on the GMP-grade quality management system platform and cell therapy manufacturing criteria.
Fully batch production and control records
Automatic separation and purification system. Image Credit: ACROBiosystems
Automatic filling equipment. Image Credit: ACROBiosystems
GMP Human IL-7 (Cat. No. GMP-L07H24) stimulates proliferation of PHA-P-activated human peripheral blood mononuclear cell (PBMC). The EC50 for this effect is 3.821 ng/mL, corresponding to a specific activity of > 1.0 × 10^8 IU/mg, which is calibrated against human IL-7 WHO International Standard (NIBSC code: 90/530) (QC tested). Image Credit: ACROBiosystems
GMP Human IL-15 (Cat. No. GMP-L15H13) stimulates proliferation of CTLL-2 cells. The EC50 for this effect is 1.004 ng/mL, corresponding to a specific activity of > 0.8 × 10^7 IU/mg, which is calibrated against human IL- 15 WHO International Standard (NIBSC code: 95/554) (QC tested). Image Credit: ACROBiosystems
ACROBiosystems is a leading manufacturer of recombinant proteins and other critical reagents to support the development of target therapeutics. The company employs an application-oriented development strategy, with a particular focus on product design, quality control, and solution-based support. Our products and services enable anyone in the field of drug development to have a more intuitive and streamlined process.
To respond to the coronavirus pandemic, ACROBiosystems has developed SARS-CoV-2 antigens specifically designed and optimized for serological test kits, including Spike-derived antigen S1, RBD, and Nucleocapsid protein. Proteins have been supplied to diagnostic companies in large quantities.
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Last updated: Aug 2, 2022 at 6:52 AM
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