drkevinryan

December 6, 2015

ASH 2015: Engineered Donor T Cells May Eradicate Progressive Disease After Stem Cell Transplant

By The ASCO Post
Here is a bottom line . Bone marrow transplants have come a long a in the treatment of acute  and chronic B cell leukemia. However many fail and the next step is to try and infuse stem cells- normal primordial cells  that have the potential to become any  or al of the cells of the marrow, This also often leads to failure as the white blood cell stem cells attack the patients cells , So, it was reasoned is there a way to manipulate infusion of whiteblodd cell stem ells So,Researchers conducted a clinical trial in which donor T cells- a powerful thinking highly essential white blood cells  were engineered to express a chimeric antigen receptor (CAR) which is a specific protein on their surface . CAR T cells are programmed to first recognize CD19, a protein on the surface of most B cells, and then attack the targeted cell. And since in relapse of B cell malignancies  Acute lymphocytic leukemia  and chronic lymphocytic leukemia are present perhaps these CART cells will attackand clean out the malignant cells from the marrow

I include this research because WE ARE MANIUPULATING THE HUMAN IMMUNE SYSTEM TO DO THE JOB IT FAILIED AT BETTER DUE TO EXPLOITING VULNERABILITIES  THE MANIPULATED CELLS WILL SEEK OUT AND DESTROY

Key Points:
  • Eight of the 20 total patients obtained remissions, including 6 complete remissions and 2 partial remissions.
  • Response rates were highest for patients with acute lymphocytic leukemia, with four of five patients achieving complete remission. The longest ongoing complete remission is more than 30 months in a patient with chronic lymphocytic leukemia.
  • No patient developed graft-vs-host disease after infusion with CAR T cells.

A study (Abstract 99) to be reported today by Brudno et al at the 57th American Society of Hematology (ASH) Annual Meeting was the first clinical trial to use engineered donor immune cells to prevent progressive cancer after stem cell transplantation. The findings were presented at a press conference during the ASH meeting.

Progressive disease is a leading cause of death after stem cell transplant. If a patient’s cancer continues to spread after transplant, the current standard treatment is to infuse the patient with unmanipulated donor white blood cells to fight the disease. However, this procedure is often ineffective and increases the risk of graft-vs-host disease.

Researchers hypothesized that instead of using unmanipulated white blood cells, an infusion of genetically engineered donor T cells would eradicate progressive disease after stem cell transplant in patients with B-cell malignancies.

Study Details

Researchers conducted a clinical trial in which donor T cells were engineered to express a chimeric antigen receptor (CAR). CAR T cells are programmed to first recognize CD19, a protein on the surface of most B cells, and then attack the targeted cell.

Patients who experienced resurgence of B-cell malignancies after stem cell transplant received a single infusion of CAR T cells obtained from each recipient’s stem cell donor. No chemotherapy or other therapies were administered.

Of 20 patients receiving the treatment, 8 obtained remissions, including 6 complete remissions and 2 partial remissions. Response rates were highest for patients with acute lymphocytic leukemia, with four of five patients achieving complete remission. The longest ongoing complete remission is more than 30 months in a patient with chronic lymphocytic leukemia.

No patient developed graft-vs-host disease after infusion with CAR T cells.

The findings support the hypothesis that infusing anti-CD19 donor CAR T cells is a promising method for treating B-cell malignancies that emerge after stem cell transplant. The investigators concluded: “Our findings point toward a future in which antigen-specific T-cell therapies will be an important part of the field of allogeneic hematopoietic stem cell transplantation

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