More Data on Granulocyte Transplant Cancer Therapies

I mentioned GIFT/LIFT, the immune cell transplant approach to cancer therapy in a short list of research that might lead to cancer cures yesterday. This line of research derives from the fortuitous discovery of a cancer-immune lineage of laboratory mice, followed by the finding that this immunity is transferable via transplant of granulocyte or other forms of leukocyte immune cells.

This discovery raises the possibility that effective cancer treatments can be established by finding donors with appropriately equipped immune cells and then transplanting those cells into patients, even in advance of a complete understanding of how this all works. That complete understanding might enable an effective cure for cancer therapy based on altering a patient's own immune cells, or a much more reliable way to determine useful donors, but it'll take much longer to get to that point, possibly decades. Thus there is considerable incentive to take the shortcut if there's one to be had, in the same way as first generation stem cell transplant therapies continue to be established usefully far in advance of the complete understanding of how they work.

You can look back in the archives for posts that cover this topic, though I should mention that the younger organizations mentioned as being involved in work on this are mostly defunct or going nowhere, it seems. Finding funding is an issue, though the Florida clinical trial partially funded by the Life Extension Foundation is apparently still ongoing. Good for them.

Today a reader pointed me to recently published research on the cancer-immune mice, which is much appreciated. Follow-on research often drifts by me, as it's harder to pick out papers from the flow once they start to focus on specific concerns and subtopics. This open access paper reinforces the previous work by Zheng Cui and others, demonstrating once more a transfer of cancer immunity between mice, but the authors note that the approach isn't as general as hoped - meaning that there are other factors at work that will make it much more of a hard slog to either (a) find a donor with immune cells that will work on your cancer, or (b) figure out how what's going on under the hood here. Why does it work for some cancers and not for others? So it's the same old story: biology is always considerable more complicated than we'd like it to be.

Immune Cells from SR/CR Mice Induce the Regression of Established Tumors in BALB/c and C57BL/6 Mice

Mouse strains that survive injection of large numbers of cancer cells are rare. Such mice constitute important experimental models for cancer resistance at the cellular and molecular levels. The spontaneous regression/complete resistance (SR/CR) mice were derived from BALB/c mice and described by Cui and colleagues in 1999. The phenotype was characterized by the ability to resist challenges from a number of cancer cell lines. This resistance involved innate immune cells, including polymorphonuclear granulocytes (PMNs), macrophages, and NK cells.

Interestingly, adoptive transfer (AT) of SR/CR leukocytes rendered recipients resistant to the intraperitoneal injection of S180 [sarcoma cancer] cells and also induced the regression of solid tumors. [In] this study we tested whether the cancer resistance of the SR/CR mice could be transferred to cancer susceptible mice by AT of selected immune cells.

In contrast to previous observations, the cancer resistance was limited to S180 sarcoma cancer cells. We were unable to confirm previous observations of resistance to EL-4 lymphoma cells and J774A.1 monocyte-macrophage cancer cells. The cancer resistance against S180 sarcoma cells could be transferred to susceptible non-resistant [mice. In] the responding recipient mice, the cancer disappeared gradually following infiltration of a large number of polymorphonuclear granulocytes and remarkably few lymphocytes in the remaining tumor tissues. This study confirmed that the in vivo growth and spread of cancer cells depend on a complex interplay between the cancer cells and the host organism.

Here, hereditary components of the immune system, most likely the innate part, played a crucial role in this interplay and lead to resistance to a single experimental cancer type. The fact that leukocytes [could] be transferred to inhibit S180 cancer cell growth in susceptible recipient mice support the vision of an efficient and adverse event free immunotherapy in future selected cancer types.

The failure to replicate early work for more than one form of cancer suggests that the underlying mechanisms here are, as mentioned above, not as general or as simple as we'd like them to be. It is very effective when it does work, however, not just causing remission of cancer, but also granting immunity. This means that research will continue, though as usual never as rapidly nor with as much funding as we'd like.


There are many kinds of cells in a single tumor - stem cells, support cells, and the rapidly dividing tumor cells.
I wonder if the granulocytes actually is able to kill ALL of the different types of tumor cells, such as the slow-dividing cancer stem cells.
I think for the granuloctyes therapy to be effective, it needs to come from multiple donors (for greater coverage) and must have a way to track that it killed not only the tumor cells, but the stem cells and support cells as well.
But I firmly believe that for every cell, someone out there has the granulocytes to kill it - too bad this therapy is halted everywhere I look.

Posted by: Yu at March 15th, 2014 7:11 PM
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