“You Can’t Start a Fire Without a Spark!!” Melanoma.. Jim Breitfeller

“You Can’t Start a Fire Without a Spark!!” anti-CTLA-4 blockage

Recent improvements in the Researcher’s understanding of the Immune System such as the role of costimulatory T-Cells and Antigen presenting cells has led to the renewal of the developmental efforts in Immunology of Melanoma. Monoclonal Antibodies (mAbs). The theory has been around about 100 years.

According to Dr. Ehrlich’s theory, the surface of white blood cells is covered with many side chains, or receptors, that form chemical links with the antigens they encounter. After binding of the specific antigen the cell is stimulated to produce more of the suitable type of receptor, which would then be shed into the blood stream as antibodies.
Antibodies, also called immunoglobulins (Ig) are proteins that are found in blood or other bodily fluids of humans, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.Antibodies are produced by a kind of white blood cell called a B cell. 1


The antibody that we are interested in is the Cytotoxic T lymphocyte-associated antigen.(CTLA-4). This antigen can inhibit T-cell responses and is involved in tolerance against self antigens. It was reported back in 1970 Bretscher and Cohn put forth the two-signal model of lymphocyte activation to explain self/nonself discrimination 6This model proposes that T-cell activation requires two independent signals. As the antigen interacts with the antibody receptor on the antigen-sensitive cell also known as the antigen presenting cell (APC) (Signal 1), it performs a conformational change which in turns paralyzes the whole cell. A new signal is now invoked (inductive signal) base on the new carrier of the antigen and antibody combined. (Signal 2) The T-cell activation not only requires the T–cell interacting with the antigen-MHC complex, but also the interaction of the CD28 receptor and the B7 as well. Once activated, the CD28 signaling leads to Interluekin-2 (IL-2) gene expression which helps promotes the immune system to propagate more T-cells.

The CD28 signaling activates the PI3 kinase and AKT pathway but they believe that there are no signal proteins involved according to Thompson and colleagues. They suggest that gycoloysis occurs along with energy metabolism causing the growth of the T-Cell.7
That T-cell is the T-Helper cell.
The AKT signaling can either lead to cell survival or programmed cell death called
Apoptosis.


It has been noted that CD4+ T-cells can be cross-prime CD8+ T-cells via IL-2.8
Once the CD8+ T-cell is activated correctly, it can deliver a hit to the tumor cells
if it can make its way passed the microenvironment of the tumor or tumors.

Happy Father's Day to all fathers who love their children and are trying to make a difference in their lives!!!!



Take Care,

Jimmy B