I would like to study the effects of immunotherapy on human GBM in vivo but not sure what is the best animal model for this purpose.
Hi Hassan,
to my best knowledge the NSG mice strain should be o.k. for your purpose, as the mice are heavily immunocompromised, lacking functional T-, B- and NK cells as well as macrophages have reduced phagocytosis abilities. Therefore both tumor cells as well as human immune cells engraft very well in this mouse strain. But be careful – over time human T cells induce a xenograft reaction somehow similar to graft-versus-host disease after bone marrow transplantation. Depending if PBMC or pure T cells are transplanted, mice become ill 4 – 6 weeks after transplanting ~ 1 Mio. PBMCs or T cells,
Cheers
Marc
You might have a look at von Bonin, Wermke et al. 2013 PLoS One. 2013 Apr 9;8(4):e60680. doi: 10.1371/journal.pone.0060680.
To be able to have an active humanized immune system in NSG mice, shall we transplant them with human bone marrow? Then the type of GBM cells we want to implant should be HLA matched with transplanted bone marrow. Am I right Sebastian and Marc?
Hi Hassan,
A good T cell-based immune response requires HLA matching but an NK response does not. Nor does a macrophage or humoral response-mediated response.
There are a number of excellent publications to help you with the question of how to humanize your mouse. It really depends on what you are trying to achieve.
In my lab, we use the BLT-NSG mouse model to generate T cells de novo from implants with fetal liver and fetal thymus along with additional fetal liver-derived CD34 cells. I know many labs that forgo the implant and prefer to use cord blood-derived CD34 cells and even others that order adult bone marrow-mobilized CD34 purchased from a company such as ALLCELLS. For experiments involving T cell-mediated killing, we definitely HLA match.
If you are lucky enough to be able to use donor matched BM-derived CD34 and GBM, awesome! If not, keep in mind that many HLA alleles are available in lentiviral vectors, which can then be used to modify your GBM so that you are not waiting for the right CD34 donor to come along.
The question of whether de novo generated or adoptively transferred T cells make it to the brains of these mice is still somewhat confounding. Many believe that due to the imperfect homology between mouse and human adhesion molecules, human T cells that extravasate to tissue sites do via "trapping" rather than homing. Nevertheless, in my experience with non-brain tissues in our BLT mice, when T cells make it to the sites of their targets, they kill quite well.
Best of luck to you!
Emily
Hi Emily,
Thanks a lot for your nice clarification. It is really helpful. I really appreciate your kind support.
Best,
Hassan
- Badges
- Science topic
- Similar topics
- Philosophy
- Philosophy Of Science
- Reasoning