Antibody-based drugs are developed as an immunotherapeutic approach to treat different types of cancer. An important step in the antibody drug–development process is the use of antibody-dependent cell-mediated cytotoxicity (ADCC) assays due to this mechanism of action for most antibody drugs. These assays require the use of effector cells, and those used most often are natural killer (NK) cells obtained from human donors and engineered cells (NK-92 and Jurkate T cells).
The different engineered effector cells types were developed with the intent to relieve the variability seen with primary NK cells. Nonetheless, there is still a need to characterize functions of the different effector cells to better determine their best use during antibody drug development. Therefore, a study was conducted to determine which ADCC effector cell type more closely represents the responses seen in humans and is more appropriate for drug development efforts.
Researchers compared the activity of three different effector cells each with two different Fc-receptor variants (V or F variant of FcγRIIIA). The test antibody used was trastuzumab because it is an antibody drug with a well-known mechanism of action in ADCC assays. The comparisons were made using the two engineered effector cell types and primary cells (NK cells also expressing V or F receptor variants) obtained from HemaCare.
Measures were made of trastuzumab affinity to receptors on the different effector cells and of ADCC activity using a breast cancer cell line. Both V and F primary cells had much higher surface receptor expression than the engineered cell types. Trastuzumab had a higher affinity for binding to the V variant of NK-92 cells when compared to NK-92 cells of the F variant cells. The ADCC activity was lower for the NK-92 cells when compared to the primary cells. The primary cells were less cytolytic than the NK-92 cell line. These results suggest that using primary cells from multiple donors in ADCC assays may be best at the early drug development stages; however, once a candidate is identified using these cells, the engineered cells should then used in the assays for more precision and quality control.
At HemaCare, we are proud to work with researchers who are devoting their time and resources to cancer research. We provide a variety of blood cell types to meet your research needs. Contact us today at 877-397-3087 to learn more.
Hsieh, Yao-Te et al. "Characterization Of Fcγriiia Effector Cells Used In In Vitro ADCC Bioassay: Comparison Of Primary NK Cells With Engineered NK-92 And Jurkat T Cells". Sciencedirect.com. N.p., 2017. Web. 19 Apr. 2017.