I'm
writing this post as I receive my first infusion in a clinical trial. I used to write about being in the chemo
chair, but the drug I'm getting today is an immunological drug, not
chemotherapy. Chemotherapy drugs kill
cells that are rapidly dividing whether or not they are cancerous. The new immunological drugs are more specific
in the cells they kill, and they kill by activating the immune system.
One
part of the immune system consists of antigens and antibodies. Antigens are molecules on the surface of a
cells. The immune system knows which
antigens are normally expressed on various types of normal cells, so it does
not react to a normal cell. However, antigens
that are not part of the normal repertoire are recognized as foreign and
attacked. Some cancer cells are so
damaged that they express proteins that are recognized as abnormal, and are
killed by the immune. The thinking is
that our bodies are constantly identifying such mutated cells and killing
them. However, some cancer cells express
antigens that allow the cells to hide from the immune system.
One
of those antigens is the PD-L1 protein.
PD stands for programmed death (apoptosis), a process that cells use to
commit suicide. When a T-cell sidles up
to a cancer cell expressing PD-L1, the protein tells the T-cell, “Hey partner, I
may look like I am broken and need to be killed, but I'm really OK.” The T-cell says, “OK, my mistake,” and goes
on to other cells without initiating programmed death. PD-L1 thus provides camouflage for the cancer
cell.
My
drug, called Tecentriq, is a lab-developed monoclonal antibody that attaches to
the PD-L1 protein masking it from the T-cell thereby allowing the T-cell to
initiate programmed death. To be
admitted to the clinical trial, I had to have a biopsy of my tumors to see if I
express PD-L1 which I do, so I am hopeful that Tecentriq will mask the protein
and kill the mesothelioma cells.
Tecentriq has been approved for bladder and urethral cancer, but there
is no guarantee that it will work with mesothelioma. Another well-known immunological is Ketruda, the
monoclonal antibody that helped cure President Carters melanoma.
Tecentriq
is given every three weeks, but I'll come in to the clinical trial center each
week at first to see how I am doing.
After the first three weeks, I will begin getting another monoclonal
antibody drug as well; however, it works on another protein that is important
to cell functioning. The basic purpose
of the study is to see how well the experimental drug works in combination with
Tecentriq. I'll write more about the
experimental drug when I begin getting it.
Over
the past six years, I have never been anxious about any aspect of my cancer
treatment; however, on my way over for my prescreening visit for the trial, I
realized that I was anxious. I think the
anxiety comes from concern about the treatments on my weakened body. I believe 58 prior infusions have damaged my
body to a certain extent. Will the new
drugs exact a toll?
There
is a concern that the PD-L1 protein is involved with human development. The DNA in every cell in the body contains
all of our genes. The differentiation of
cells into heart cells, lung cells, etc. involves turning different genes on or
off shaping the cells to do their job in the body. PD-L1 may be used in development to signal to
the immune system that even though a cell looks abnormal it is a normal cell
for a certain type of tissue. Something
I don’t understand is whether mature differentiated cell still express PD-L1. Will the Tecentriq unmask PD-L1 expressing
normal cells and allow them to be killed like the cancer cells? It may be that some of the possible side
effects of the drug result from such action.
However, I read articles and drug package inserts online, and the drug
seems generally to be tolerated well, and I will be under close scrutiny while
in the trial. I feel better about the
risk now, although there is always a risk in a clinical trial.
My
infusion is over for today, and all appears to have gone well. Now all I have to do is hang around for checks
of vital signs and a blood draw to measure the concentration of the drug in my
blood. Unfortunately, the nurse will
have to draw the blood from a vein because the drug went in through my port and
might contaminate the blood draw.
More
to follow when I get the other drug or if anything of note happens.
David
PS it is now nine hours later, and I have had no
noticeable reaction to the infusion. So
far so good.
