Spontaneous Regression of Advanced Cancer in Mice after White Blood Cell Transfer

Here we have some absolutely fascinating research from the Wake Forest University School of Medicine. It involves the SR/CR Mouse model, originally discovered at Wake Forest University in 1999, with a special ability to resist cancer. The animal originally was involved in an experiment in which aggressive sarcoma cells were injected into mice (all mice were members of the highly inbred strain BALB/c) and progress of the neoplasm was studied. The SR/CR line of mice has shown resistance not only to sarcoma, but also to leukemia, lymphoma, liver cancer, and lung cancer, according to Wake Forrest. Furthermore, when cross-bred with other mice types, the resistance to cancer was shown to be genetically encoded (likely a single mutation in a single gene, with a dominant expression.)
Scientists at Wake Forest University have studied this animal model extensively, demonstrating in the process that cancer resistance is what it is, and not just a rejection of the foreign tissue (seen in the organ transplantation.) They have also demonstrated that these SR/CR mice havf normal life spans and no evidence of increased autoimmune disorders.
What’s making the headlines now is the evidence of “adoptive transfer,” reported in the latest Proceedings of the National Academy of Science, in which scientists have demonstrate the ability to cure cancer in normal mice by transferring purified immune cells (white blood cells) from SR/CR mice. From the press release (a must-read account of fascinating research!):

Even though our in vitro (test tube) experiments suggested that the innate immune cells themselves were responsible for tumor killing, it was still possible that this killing might only work if the rest of the mouse also expressed the same mutation. Therefore, we placed cancer cells and immune cells from spontaneous remission/cancer resistant (SR/CR) mice together in a normal mouse to determine whether the cancer cells could survive. Without the SR/CR immune cells, such cancers grow rapidly in normal mice and the mice die in 3-4 weeks. But, when these cancer cells were injected together with the SR/CR immune cells, the tumor was killed. Thus, the environment in a normal mouse still allowed these cells to work. This suggests that no other cell type or soluble factor in the mice is required to allow the immune cells to function and kill cancer.
A more difficult experiment was to inject a normal mouse with cancer cells and allow the tumor to implant and grow, then inject the SR/CR immune cells at a later time. Again, the mutant immune cells killed the cancer cells selectively, without harming the normal mouse. Finally, we performed the most difficult challenge (shown in Figure 5), which was to inject the normal mice with cancer cells at one site (e.g., subcutaneously on the back), and then later inject the SR/CR immune cells at another site (e.g., intraperitoneally or into the abdomen). This meant that the injected immune cells would have to migrate to the tumor and kill it at a distant site, all the while being in a normal mouse tissue environment. Surprisingly, this strategy worked, and the established cancer in the normal mouse was killed by the SR/CR immune cells injected elsewhere. Initially, the cancers on the back actually appeared to get slightly bigger after the immune cells were injected into the peritoneal cavity, but after a few days the cancer began to shrink. The initial swelling may reflect an initial influx of active white blood cells into the tumor. The cancers disappeared completely in two weeks. As controls, other mice injected with similar immune cells from a normal non-resistant mouse showed no tumor shrinkage, and all of these control mice died at the expected time. The surviving recipient mice were “cured” of their tumors (the tumor never recurred, even after a year – half a lifetime in mouse terms). Thus, we can say with confidence that the killing of cancers by the SR/CR immune cells requires only the immune cells (and not something else) and is remarkably tumor-specific without causing significant harm to normal tissues…
The types of white blood cells we injected into the normal mice are thought to have a rather short lifespan (a few days or weeks). Thus, we were surprised to see continued cancer resistance in the normal mice for months after they received SR/CR white blood cells. There is more than one theoretical way in which this could happen, but one which we favor is that the purified white blood cells we injected contained a small fraction of stem cells, and that these gradually became part of the mouse’s immune system. Since we did these transfer experiments between SR/CR and normal mice of the same inbred strain, this is not entirely unexpected. By performing these experiments using immune cells from a male SR/CR mouse and transferring them into a female recipient normal mouse, the injected immune cells could be identified later, because they contained a “y” chromosome. In this way, we were able to show that some of the injected immune cells survived for a very long time and were probably involved directly in killing the distant cancer.

Read the whole thing: highly recommended!