Good news! Cancer is history (soon)!
"Two teenagers with an aggressive form of leukaemia have been successfully treated with T cells that were engineered to fight cancer without targeting healthy T cells. Healthy donor T cells were engineered using CRISPR-Cas9 gene editing to include a chimeric antigen receptor (CAR) gene, which helped the immune cells to target cancer. To prevent these CAR T-cells from also harming healthy T cells, three genes were inactivated using base editing, in which a single alteration is made in the DNA code. Two of three children treated were in remission within 28 days. The third child responded to the treatment but died of a fungal infection."
"In a first, scientists have used a DNA-altering method called base editing to treat disease — in this case, by modifying immune cells to successfully treat two teenagers with an aggressive form of childhood leukaemia. ..."
From the abstract:
"BACKGROUND
Cytidine deamination that is guided by clustered regularly interspaced short palindromic repeats (CRISPR) can mediate a highly precise conversion of one nucleotide into another — specifically, cytosine to thymine — without generating breaks in DNA. Thus, genes can be base-edited and rendered inactive without inducing translocations and other chromosomal aberrations. The use of this technique in patients with relapsed childhood T-cell leukemia is being investigated.
METHODS
We used base editing to generate universal, off-the-shelf chimeric antigen receptor (CAR) T cells. Healthy volunteer donor T cells were transduced with the use of a lentivirus to express a CAR with specificity for CD7 (CAR7), a protein that is expressed in T-cell acute lymphoblastic leukemia (ALL). We then used base editing to inactivate three genes encoding CD52 and CD7 receptors and the β chain of the αβ T-cell receptor to evade lymphodepleting serotherapy, CAR7 T-cell fratricide, and graft-versus-host disease, respectively. We investigated the safety of these edited cells in three children with relapsed leukemia.
RESULTS
The first patient, a 13-year-old girl who had relapsed T-cell ALL after allogeneic stem-cell transplantation, had molecular remission within 28 days after infusion of a single dose of base-edited CAR7 (BE-CAR7). She then received a reduced-intensity (nonmyeloablative) allogeneic stem-cell transplant from her original donor, with successful immunologic reconstitution and ongoing leukemic remission. BE-CAR7 cells from the same bank showed potent activity in two other patients, and although fatal fungal complications developed in one patient, the other patient underwent allogeneic stem-cell transplantation while in remission. Serious adverse events included cytokine release syndrome, multilineage cytopenia, and opportunistic infections.
CONCLUSIONS
The interim results of this phase 1 study support further investigation of base-edited T cells for patients with relapsed leukemia and indicate the anticipated risks of immunotherapy-related complications."
A CRISPR-based method makes T cells that thwart teens’ cancer A technique called base editing has been used for the first time to treat human disease.
Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia (no public access)
No comments:
Post a Comment