Saturday, March 8, 2014

Progress in leukemias with the CAR-T Cell

Genetically engineered autologous T cell fight blood cell cancers seem to attract attention of researcher lately. these cell work with CD19 and include a viral component.   Chimeric Antigen Receptor-T or CAR-T has been reported to represent another ex-vivo preparation of the patient own T-Cell genetically engineered to attack a new cancer cells notoriously resistant such as those of Acute Lymphoblastic Leukemia and Burkitt disease.   In the heels of Ibrutinib, this appears to be a major advance in cancer therapy.

Van Zelm et al:
"The CD19 protein forms a complex with CD21, CD81, and CD225 in the membrane of mature B cells. Together with the B-cell antigen receptor, this complex signals the B cell to decrease its threshold for activation by the antigen."
In a way disruption of CD19, may also lead to trouble in this complex formation.
previous investigations had suggested that disruption at CD80, 81 could be used in Ovarian cancer treatment.  Therefore such a complex could be important indeed as more technologies are being developed.  These new developments are  strengthening the Immunologic option in both solid and hematologic cancers.

Other function of CD19

Watanabe et al:

"CD19 serves as a positive B-cell response regulator that defines signaling thresholds critical for B-cell responses."

Chen et al:

" Conditional deletion of Foxo1 in B cells resulted in an increased percentage of marginal zone B cells and a decrease in follicular B cells. In addition, Foxo1 deficiency corrected the absence of marginal zone B cells that occurs in CD19-deficient mice. These findings show that Foxo1 regulates the balance of mature B cell subsets and is required for the marginal zone B-cell deficiency phenotype of mice lacking CD19."

This further point to the strength of CD19, that is despite the fact that it has a role in a complex to orient cellular functions, it also lead to malformation as it determine what scientist call morphologically a "Marginal zone". Any gene affecting structure shape has been one of our criteria for importance.  And clearly, immunologic deficiencies are characterized by congenital malformations.

May be this CAR-T will actually have the most effect here ...in the Marginal Zone!
The patient’s own T-cells are extracted and genetically engineered ex vivo to target the CD19 antigen present on cancer cells; a viral vector is inserted, and the cells are reinfused into the patient via a single infusion where they are designed to expand and attack cancer cells like a “smart bomb.” Currently, it takes approximately 10 days to engineer the cells.
“It looks like the disease has disappeared after a single infusion of these engineered T-cells,” reported James N. Kochenderfer, MD, from the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI).
- See more at: http://www.valuebasedcancer.com/article/novel-car-t-therapy-shows-impressive-results-aggressive-leukemia-lymphoma#sthash.I8Q2ynHK.dpuf
The patient’s own T-cells are extracted and genetically engineered ex vivo to target the CD19 antigen present on cancer cells; a viral vector is inserted, and the cells are reinfused into the patient via a single infusion where they are designed to expand and attack cancer cells like a “smart bomb.” Currently, it takes approximately 10 days to engineer the cells.
“It looks like the disease has disappeared after a single infusion of these engineered T-cells,” reported James N. Kochenderfer, MD, from the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI).
- See more at: http://www.valuebasedcancer.com/article/novel-car-t-therapy-shows-impressive-results-aggressive-leukemia-lymphoma#sthash.I8Q2ynHK.dpuf
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