Page 8 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

1.4 Cancer therapy and immunotherapy 5

cancers are caused by viruses and cancer vaccine may, thus, be useful for these kinds
of tumors [28]. A genetically engineered oncolytic herpes simplex type 1, which
secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), has been
used for cancer therapy. This immunotherapeutic approach has had beneficial effects
in the eradication of head and neck squamous cell carcinoma and melanoma [29].
One more approach is using mAbs which block T cell checkpoints role to regulate T
cell responses. CTLA4 is a significant inhibitory receptor that has regulatory effect
on T cell function and plays an important role in the priming phase of the immune
response. This molecule is expressed on T helper and T cytotoxic cells, as well as
on FOXP3+ regulatory T cells [30]. Administration of mAbs by targeting human
CTLA4 has improved survival in patients with metastatic melanoma [31]. Another
mAbs blocking other T cell checkpoints, such as the programmed cell death pro-
tein 1 (PDCD1/PD1), V-set domain-containing T cell function inhibitor 1 (B7x),
programmed cell death ligand 1 (PDL1/CD274), CD276 (B7H3) antigen, and B,
T lymphocyte attenuator, have also been used in clinical trials. Furthermore, some
investigations have indicated a significant therapeutic effect in some kinds of tumors,
including ovarian cancer, nonsmall cell lung carcinoma, melanoma and renal cell
carcinoma [32]. PDL1 expression by tumor cells has been reported to be associ-
ated with poor clinical outcomes and may be accompanied with clinical response
to anti-PD1 and anti-PDL1 treatment. On the other hand, PDL1 inactivate tumor-
infiltrating cells and regulatory T cells (T cells) have an immunosuppressive role
reg
in the tumor microenvironment [33]. Additionally, the combination of these agents
with anti-CTLA4 and other immunotherapy approaches has led to promising results.
The combination of cancer vaccines with factors targeting the IL-12 receptor has
resulted in contradictory results. This may be because of the upregulation of IL-12
receptor by both activated T effector cells and T cells [34]. Therefore, new strate-
reg
gies focused on more specific targeting of T cells which decrease their immunosup-
reg
pressive effects are needed. Adoptive T-cell therapy has been qualified as an efficient
treatment for cancer immunotherapy in early phase clinical trials. In this approach, a
large quantity of tumor-specific T cells derived from peripheral blood or preferably
from the tumor niche is transferred to patients with established tumors [35]. Based on
reports, a combination of chemotherapy and immunotherapy has beneficial effects
and in future chemoimmunotherapy is an attractive method [36]. These combination
methods could be Toll-like receptor (TLR) signaling pathway agonists/antagonists,
cytokines, mAbs targeting T cell checkpoints and cancer vaccines [37]. In addition,
radiation and radiofrequency ablation can be other combination therapy with immu-
notherapy [38]. Although immunotherapy and its combination with other therapies
such as radio immunotherapy may be useful for tumor treatment, there are many
limitations to consider.
Patient definition as an optimal target, optimal biological dose, and timetable,
need for better trial designs including appropriate clinical endpoints, and identifica-
tion and validation of predictive biomarkers are just a few to mention [27].
By proliferation of cancer cells, the formation of the orchestrated enzyme
required for proper metabolism of its various components may become unbalanced