Immunotherapy and Cancer: Harnessing the Power of Diagnostic Assays - 8

Immunotherapy and Cancer | Harnessing the Power of Diagnostic Assays

Box 1: Immuno-Oncology Drug Classes
The recent focus on the development
of immunotherapies has resulted
in a long list of relatively new and
emerging drugs. Among them are:
ADOPTIVE CELL THERAPIES
* T-cell receptor. T-cells with the most cancer-fighting potency are selected, grown
into the billions, and reinfused into the
patient.

* CAR-T. Chimeric antigen receptor (CAR)
T-cell therapy involves removing T-cells
from a patient's blood, inserting a gene into
the T-cells for a receptor that binds to the
patient's cancer cells, growing the resulting
CAR-T cells to large numbers, and reinfusing
them into the patient.
ANTIBODIES
* Monoclonal Antibodies (mAbs). Monoclonal antibodies are designed to bind to
specific antigens on cancer cells.

* Bispecific Monoclonal Antibodies
(bimAbs). Bispecific mAbs are ones in
which one binding site is designed to attach
to a cancer cell and another is designed to
attach to T-cells.

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CHECKPOINT INHIBITORS
Approved
* CTLA-4 inhibitors. Cytotoxic T-lymphocyte-associated (CTLA) protein 4 (CTLA-4)
is a protein on T-cells that acts as an "off"
switch.

* PD-1 inhibitors. Programmed death
receptor 1 (PD-1) is a checkpoint protein on
T-cells.
* PD-L1 inhibitors. Programmed death-ligand 1 (PD-L1) is a protein on normal (and
some cancer) cells that, when it binds PD-1,
inactivates the T-cells.

Chimeric antigen receptor (CAR) therapy: Engineered
receptors on the surface of a T-lymphocyte bind
specifically to CD19-antigen molecules on the surface
of a leukemia cell.

Emerging
* GITR inhibitors. Glucocorticoid-induced
TNFR family related gene (GITR) inhibitors
prevent T-cell inactivation while activating
CD8+ T effector cells.

CYTOKINES directly stimulate immune effector cells and stromal cells at the tumor site and
enhance tumor cell recognition by cytotoxic
effector cells.

* LAG-3 inhibitors. Lymphocyte activation
gene 3 (LAG-3) inhibitors work in a similar
way to GITR inhibitors.
* 4-1BB stimulators. Tumor infiltrating lymphocytes have an array of co-stimulatory
receptors (those involved in activating T-cell
response). 4-1BB is one of them.
* CD40 stimulators. Cluster of differentiation
40 (CD40) is also a co-stimulatory protein.

ONCOLYTIC VIRUS THERAPIES (VACCINES).
Cancer vaccines involve modifying viruses so
that they reproduce efficiently in cancer cells
until the cell bursts, but do not impact healthy
cells.
ANTIBODY-DRUG CONJUGATES are monoclonal antibodies that target a tumor-specific antigen
and carry a potent drug that is released once inside
the cell.

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