New System Developed for Studying B-cell Cancers

Diffuse large B-Cell lymphomas (DLBCL) are cancers that can occur in both dogs and people. Unfortunately, the search for effective treatments is complicated by the fact that these cancers are very difficult to study in the lab. Actual DLBCLs are made up of highly variable collections of cells, but the cell lines currently used to study such cancers do not reflect that diversity. Such cell lines are created in a very controlled way. Furthermore, once refined from the few cells that survive the transformation process, they are also fairly homogeneous. Therefore, they may not be a particularly accurate system in which to search for effective DLBCL treatments.

That’s why, with the help of the AKC Canine Health Foundation, Dr. Daisuke Ito and colleagues set out to find an alternative to traditional cell culture techniques for studying DLBCLs. Instead of creating a DLBCL-like cell artificially, using viral infection, they wanted to find a way to grow and maintain the diverse collection of B-cells found in an actual canine cancer. To do this, they attempted to leverage the special properties of a protein known as CD40L, which had previously been shown to support the growth of cancerous B-cells in the lab.

In their newly developed system, the scientists used a special type of engineered human cells, known as KtCD40L, to supply CD40L to tumor cells harvested directly from dogs diagnosed with B-cell lymphomas. Although canine B-cells normally died within a day or two when grown alone, when mixed with the special feeder cells, they thrived. More importantly, they maintained many of the characteristics of the tumor from which they’d been grown.

Even more importantly, the scientists discovered that they didn’t actually need the KtCD40L feeder cells to keep the tumor cells alive, at least not in the short term. All they needed was soluble CD40L! By simply including the protein in the culture medium, they could grow malignant canine B-cells for future study. This gave them the ability to create collections of tumor cells that could easily be used to test potential cancer treatments for efficacy, without needlessly exposing animals to an ineffective drug.

The development of such a straightforward, efficient method of culturing primary B-cell cancers may be just what scientists need to gain a better understanding of both human and canine DLBCLs. However, and perhaps more urgently, the techniques described by Dr. Ito and colleagues can also give doctors and scientists a safe and efficient way to see how well new therapeutic agents will work in individual patients with these cancers. Testing the efficacy of drugs on the very cancer cells they are intended to treat could help doctors pick the best therapy for any given patient, while reducing patients’ exposure to potentially toxic treatments that would not have been effective against their disease.

This work was funded by AKC Canine Health Foundation grants 615 and 1113.