Ø CAR(Chimeric
Antigen Receptors) T-CELLS:
Definition:
CAR T-cells are
those T cells in which we insert the gene for Chimeric Antigen Receptor (CAR)
and these receptors are then displayed on CAR T cells surfaces.
Ø CHIMERIC T
CELLS RECEPTORS:
Definition:
Chimeric T
Cells receptors are those recombinant Receptors that provide both antigen
binding and T-cells activating functions.
Ø CAR T-cells
THERAPY:
Definition:
A type of
treatment in which the gene for a specific
receptors called CAR are inserted into T cells in order to modify them
invitro is called Chimeric Antigen Receptors T therapy.
Ø CAR T-CELLS
THERAPY STEPS:
1.
Blood from the
vein in the patient’s arm is collected and flows through a tube to apheresis
machine.
2.
This machine
removes the White blood cells from the blood including T cells .
3.
The rest of
blood excluding T cells is sent back to the patient.
4.
Now the gene
for special receptors called Chimeric antigen receptors (CAR) is inserted into
T cells in vitro.
5.
Millions of CAR
t cells are grown in the lab and given to patient by infusion.
6.
These CAR t
cells can bind to antigen on cancer cells and kill them.
Ø ADVERSE EFFECTS
OF CAR T-CELLS THERAPY:
1.
Cytokine-release
Syndrome (CRS): A serious side effect associated
with Chimeric antigen receptors T-cells therapy is CRS. CRS is the result of
T-cell activation. CRS may result in high fever, headache, low blood pressure.
2.
B-cells
Aplasia: T-cell
therapy targeting antigen (found on B-cells surface) not only destroys
cancerous B cells but also normal B cells. Hence, B-cells absence results in
low production of antibodies.
3.
Tumor lysis
syndrome: It
is a group of metabolic complications that can occur due to breakdown of dying
cells (cancerous cells). TLS can threat life.
Ø BENEFITS/ADVANTAGES:
CARs don’t require the antigen processing
and presentation by HLA( Human leukocytes antigen) and are therefore
applicable to HLA-diverse patient population.
CARs
provide a wider range of functional properties than transduced T-cell
receptors (TCR), where strength
of signaling, which is
for the most
part determined by
the TCR’s attraction for antigen, is the principal
cause of T-cell fate.
This therapy utilizes body’s own immune
system to fight cancer.
Ø ADVANCEMENT IN
CAR T-CELLS THERAPY:
FDA
Approvals:
Recently, two
different CD19 CAR T-cell products got FDA approval.
1.
Tisagenlecleucel
(Kymirah) : The first CAR
T-cell product to be approves and is used to treat B-cell acute lymphoblastic
leukemia (B-ALL).
2.
Axicabtagene
ciloleucel (Yescarta) : After the few months of
approval of Kymirah, another CAR T-cells product was approved that is
used to treat adult refactory diffuse
large B-cell lymphoma .
Ø FUTURE GOALS OF
CAR T THERAPY:
CAR T-cell
therapy has got preliminary approval for
treatment of children and young adults with a specific form of leukemia that has not been cures with
chemotherapy.
