Allogeneic hematopietic stem cell transplantation (HSCT)
HSCT generally involves transferring the hematopoietic cells from an immunologically compatible healthy person (the donor) to a pateint after a conditioning regimen. Healthy hematopoietic stem cells (HSC) can replace the damaged hematopoietic tissue of a patietn, and specific donor derived immune cells can have a therapeutic effct on cancer, infections, and immunoglogical diseases. US Patent 10,857,183
Dimov (US 10,857,183 and 10,300,090) discloses a method of treating a disease that includes administering a cell population which include HSPC along with T memory, Treg and naive conventional alphabeta-T cells at various concentrations. The HSPC refers to hematopoietic stem cells that express increased levels of phenotypic markers CD34, CD133 and CD90. The method also includes a method of producing the various populations. For example, a sample can be contacted with a binding molecule for CD34 to enrich for CD34+ cells, recovering the popuation of CD34 depleted which are then contacted with a molecule tht binds CD25 to enrich for CD25+ cells and CD25-depleted cells which are then contacted with a molecule that binds CD45RA to enrich for CD45RA+ and CD45RA depleted cells. The population enriched for CD34+ cell, CD25+ cells and CD45 depleted cells can be formulated as a therapeutic formulation. The cell populations have been sculpted to enrich the number of cells with therapeutic benefit and deplete the cell populations that are detrimental in a graft recipient.
HSCT Conditioning Mediums:
Donor-derived (allogeneic (allo-) hematopoietic stem cell transplantation (HSCT) can be curative for a diverse array of genetic and acquired hematological conditions including bone marrow failure (BMF), hemoglobinopathies and malignancies. However, allo-HSCT protocols rely on DNA damaging total body irradiation (TBI) and/or chemotherapy based conditioning, which results in short and long term toxicities and predispose patients to secondary malignancies. As an alternative, a new protocol that uses a TBI and buslfan free antibody containing conditioning regimen that includes briquillimab, an aglycosylated humanized mAb that blocks CD117 (also known as c-KT), a surface receptor tyrosine kinase expressed on hematopoietic stem and progenitor cells (HSPc) combined with rabbit anti-thyjmocyte globulin, low-dose cyclophosphamide, fludarabine and rituximab immunosuppression to prevent immunolgogical rejection and EBV reaction has been described. Patients tare then transplated with TCRalphabeta+ T cell depleted and CD19+ B cell depleted HSPCs (alphabeta-depleted HSPCS), a stem cell therapy that enahcnes donor hematopoietic and immune resconstiution, dereases graft veruss host disease (GvHD) and explands the donor pool, enablishing the use of more immune disparate donors. (“Irradiation and busulfan-free stem cell transplantation in Fanconi anemia using anti-CD117 antibody: a phase 1 b trail” Nature Medicine, 2005).
–Briquilimab is an investigational, humanized monoclonal antibody that targets the c-Kit (CD117) receptor, which is found on the surface of mast cells and hematopoietic stem cells. It works by blocking the binding of stem cell factor to its receptor, which can lead to mast cell depletion and the elimination of hematopoietic stem cells. Briquilimab is being developed for two main purposes: as a conditioning agent to prepare patients for stem cell transplants and as a standalone therapy for mast cell-driven diseases like chronic urticaria.
Regenerative Medicine as an Alternative to Traditional Transplantation:
Implanting cells into Lymph Nodes:
–regenerating functional livers using lymph nodes:
Companies are working on harnessing a body’s natural regnereative capabilities by implanting hepatocyte (liver cells) into lymph nodes. The hepatocytes self-orgnaize and grow, forming functional liver tissue within those lyph nodes. The new liver tissue can perform essential metabolic funcitons, providing therapeutic benefits for individuals with liver disease or failure. One key advantag eo fhis technology is an ability to create ectopic organs separate form a diseased liver. The approach reques no invasive surgical procedures typically associated with traditional organ transplantation. Hepatocytes are injected into patients using endoscopy ultrasound (EUS), a minimually invasive approach for patietns with end stage liver disease, into a lymph node located in the upper abdomen.