Page 75 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

4.1 Cancer immunotherapy 73

development of adequate numbers of antitumor T cells with the functions essential to
mediate cancer eradication. Perhaps the most important point, using this approach is
allowing the manipulation of the host before a cell transfer in order to create a more
suitable microenvironment that is advantageous in supporting antitumor immunity.
ACT does not only consist of engineered CAR-T cells, but also other types of
ACT including endogenous T cell (ETC) and tumor-infiltrating lymphocyte (TIL)
therapy. With the use of these methods, ACT has been utilized to treat a variety of
cancers including melanoma, cervical cancer, lymphoma, leukemia, bile duct cancer,
and neuroblastoma [8].

4.1.3.1 CAR
The main restriction of the effective use of ACT is the recognition of cells that can
target antigens selectively expressed on the tumor and not healthy cells.
In the lab, a specific receptor which was planned to bind with predetermined pro-
teins on tumor cells was produced. The CAR is then attached to T cells. This aids the
T cells to detect and kill tumor cells that have the defined protein that the receptor is
set to bind with. These modified T cells (CAR T cells) are then proliferated in large
numbers in the lab and conveyed to patients with cancer. The FDA-approved CAR
T cells are made of an extracellular single chain Fv (scFv) antibody fragment led
against the B cell-specific antigen CD19, the transmembrane domain and intracel-
lular TCR activation and co-stimulatory domains [9].

4.1.3.2 ETC
ETC therapy developed as a treatment strategy where endogenous tumor-reactive T
cells can be found in the peripheral blood of patients, isolated and proliferated while
keeping antitumor activity. Some groups have been recapitulated in vivo biology of T
cell induction, using autologous APCs (e.g., DCs) or artificial APCs that can convey
an antigen-specific TCR signal along with essential costimulatory ligands to enhance
the number of low frequency antigen-specific T cells in the blood. The use of TCR in
the peripheral blood creates a broader net in obtaining scarce antigen-specific T cells,
many of which are targeted to a shared tumor-associated self-antigen, and unlike TIL
therapy, does not necessitate TIL-rich samples which may not be available or may be
difficult to surgically access.
Another biological benefit to the utilization of peripheral blood as a source of
effector T cells is:

• The capacity to produce longer lasting T cells from a nonmanipulated
population
• Making a rich source of extremely replicative, ‘helper-independent’ central
memory type CTL
The use of this approach has exhibited clinical efficiency in the treatment of
patients with refractory metastatic melanoma and other solid tumor malignancies,
albeit in relatively few trials.