It’s not every day you see a small drug company’s presentations get picked for both the plenary session and the late-breaker session at a conference, but Syndax Pharmaceuticals Inc. managed to do just that at the 65th American Society of Hematology Annual Meeting 2023 – with a little help from a friend.
Avoidance of graft-vs.-host disease (GVHD) after a hematopoietic stem cell transplant could depend on certain members of the microbiome. According to a study led by scientists at the Fred Hutchinson Cancer Center (FHCC), while some species of intestinal bacteria repressed the expression of the major histocompatibility complex II (MHC-II), others induced it and triggered the immune response that produces GVHD.
A single low-dose injection with anti-DLL4 in a nonhuman primate model of acute graft-vs.-host disease (aGVHD) dramatically improved post-transplant survival, providing durable protection from otherwise lethal gastrointestinal GVHD, researchers reported in the June 28, 2023, issue of Science Translational Medicine. Blocking DLL4 specifically increased the migration of beneficial regulatory T cells into the intestines, with concomitant reduction in effector T cells, which are the main culprits in aGVHD. Ultimately, these activities effectively provided protection against T-cell-mediated damage in a nonhuman macaque primate model.
Allogeneic mesenchymal stromal cell (MSC) therapy is well tolerated in patients with graft-vs.-host disease (GVHD) but results in clinical trials have shown that it lacks potent immunosuppressive effects. Researchers from the Mayo Clinic thus proposed enhancing MSC immunosuppression by bioengineering the first chimeric antigen receptor (CAR) MSCs (CAR-MSCs) and targeting E cadherin (anti-Ecad CAR-MSC), with a CD28 intracellular signaling domain to induce antigen-specific immunosuppressor effect.
Nuclear body protein SP140 is mainly expressed on immune cells such as B and T cells, monocytes or dendritic cells and they are activated by interferon and regulated upon cellular stress, such as during viral infections.
Researchers from Caribou Biosciences Inc. presented preclinical data for the novel BCMA-specific allogeneic CAR T-cell therapy candidate, CB-011, being developed for the treatment of relapsed or refractory multiple myeloma. A genome editing strategy was implemented in the production of CB-011 to blunt CAR T-cell rejection by both patient T cells and natural killer (NK) cells.
When oxygen levels of the intestine increase, the appropriate hypoxic conditions for intestinal microbiota are lost. This state may be caused by immune-mediated malfunction of the intestinal epithelium. By controlling oxygen levels, the imbalance in the intestinal microbiome (dysbiosis) can be reduced.
