Re: NEJM video on T-Cell Pancreatic
So this comment about dosing of IL-2 is a critical one to appreciate. Early in developing IL-2 high doses were given with very high toxicity /adverse events. Low dose IL-2 had weake/negligible effects. So frequent low doses are a compromise to maintain a constant presence of Il-2 to maintain the effector functions of killer cells. If the even briefly these effectors live in a low IL-2 environment they shut down. The biology here is key. The best tumor rejection is a combination of IL-2 producing CD4 T cells and CD8 killers in the same space at the same time. Supply meets demand. There is a large body of evidence in both immune rejected transplants and tumors showing a clear need for both cell types in the infiltrate. Personally I have looked at (prepared and examined) both rejected kidney transplants (oh so long ago) and looked at rejected tumors from mouse models and seen this first hand. In designing tumor vaccines it has become clear that vaccines MUST contain HLA Dr (class 2 binding 15 MERS) sites for CD4 helpers and distinct (or embedded) class I HLA binding sites (9 MERS) . Either one alone does not really work. A variety of vaccine designs Iíve worked with (designed or licensed) are based on the two cell concept.
Many moons ago back in the Biomira days we bought a small liposome technology company (Princeton spin out folks from the liposome company, my friend Mircha Popescu was founder, crazy crazy good scientist) that was developing a liposomal delivery slow release IL-2 drug. I loved it. The company clinical VP didnít and they dropped it. Huge huge mistake. The decision was based on the early history of adverse events and the fear of getting shut down over it. Huge mistake. A slow release IL2 drug today would be the bomb. Heck just 25 years early I guess. But take note of this issue. Itís a big deal