Our scientists are always looking to improve the usability and functionality of our immune cells. We strive to be more than just a supplier – we want to help our customers get the most out of their experiments to advance their research efforts.
So when a customer came to us with a question, we became curious as well and offered to do the research ourselves and share the findings. In 2014, Wang et al. published a study investigating in vitro characterization of the anti-PD-1 antibody nivolumab using our CMV-positive PBMCs and lysates of CMV-infected cells. Our customer was having some difficulty with the methods used in the publication and wanted to conduct a similar experiment using a T cell line in hopes of improving the reproducibility of the data.
For an overview of our research and findings, view the infographic below. The BC3 cell line used in our research is a line of CD4+ T cells specific for a peptide of myelin basic protein, which can be purchased on our website. We have several BC3 cell lines in stock.
Findings: PD-1 Blockade Enhances In Vitro Responses
1. Antibody to programmed cell death protein (PD-1) enhances in vitro response of primary T cells but not cultured T cell lines.
Our research did answer our customer’s original question of whether she can use a T cell line to improve the reproducibility of the data from Wang et al. The cultured T cell line did not produce a response in vitro, but did lead us to another question: Why aren’t the cultured T cells influenced by nivolumab the way that primary T cells are? Further research is needed to explore this subject.
2. Resistance to anti PD-1 is observed regardless of the level of PD-1 expression.
The cultured T cells we used (both CD4+ and CD8+) express PD-1. Since nivolumab binds to PD-1, it ought to work in this system.
3. Use of cultured T cell lines may allow improved understanding of immune checkpoints.
Between 2014–2016, nivolumab received FDA approval for the treatment of BRAF V600 wild-type, unresectable or metastatic melanoma; metastatic squamous non-small cell lung cancer; metastatic non-small cell lung cancer; advanced renal cell carcinoma; and classical Hodgkin lymphoma.
However, nivolumab does not work for all patients, which may reflect the characteristics of the patient’s T cells, among other factors.
As the opportunity arises to further experiment on the effects and uses of nivolumab, we will post an update to the blog.
Dr. Lodge is a member of the AAI and presented this research at the American Association of Immunologists Annual Meeting, Immunology 2016, May 13-17, 2016 in Seattle. A copy of the abstract can be found in the Journal of Immunology.