Page 107 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

4.7 Nonspecific immunotherapy 105

there is a need to inject the cytokines in order to amplify tumor-specific immune
responses near to other treatments like a vaccine to produce a highly efficient effect.
The most common ones are discussed here.
4.7.1.1 Interleukins
Interleukins is a cytokine group that acts in signaling between cells such as white blood
cells and regulate cell growth, differentiation, and motility [104]. Each interleukin has
its own role and they have a different effect on the immune system. Studies on animal
tumor model have demonstrated that some cytokines especially interleukins have a
broad antitumor activity which this feature has made cytokine-based approaches for
cancer therapy. In 2015, Tugues et al. have demonstrated the therapeutic effects of
IL-12 and have highlighted the advantage of the antitumor activity of IL-12 with its
limited adverse effects that make this interleukin as a potent cytokine in mediating
antitumor activity in a variety of preclinical models [105]. Other interleukins like
GM-CSF, IL-7, IL-15, IL-18, and IL-21 have been entered clinical trials for patients
with advanced cancer but most of them are used as an adjuvant not a single treatment. To
date, Interleukin-2 (IL-2) has got FDA approval as a single agent for cancer treatment.
4.7.1.2 Interleukin-2
In 1980 IL-2 because of its ability to expand T-cells and sustaining T cell responses
has been known as a powerful immune growth factor. IL-2 expands T cells without
loss of functionality. This effect has caused the cytokine to be used in cancer immu-
notherapy. While immune-related adverse effect has been reported, but it has been
demonstrated that IL-2 leads to complete and curative regression in the patients with
cancer [106].
IL-2 also plays an important role in growth and activation factor for natural killer
(NK) cells. IL-2 has a role in T cell proliferation, differentiation and activation.
IL-2 with anti-IL-2 have a powerful signaling ability with the intermediate affinity
CD122/CD132 receptor in vivo.
These promising outcomes make this cytokine as a single treatment in cancer
immunotherapy. And now a man-made version of IL-2 [Aldesleukin (Proleukin)]
has been produced in the laboratory and has been approved to treat advanced kidney
cancer and metastatic melanoma.
IL-2 can be used as monotherapy. However, scientists have shown that high doses
of IL-2 have adverse effect, hence it can be combined with another cytokine such as
Interferon-Alfa or other cancers therapy like chemotherapy or radiotherapy. IL-2 also
is used with other immunotherapy like adoptive cell transfer regimens, antigen-spe-
cific vaccination, and blockade of ICI molecules which can turn them more efficient
against some cancers, but the side effects of the combined treatment are also increased.
IL-2 has showed a profound effect on cancer treatment. However, it has some
side effects including chills, fever, and fatigue. Proleukin also has side effect such
as gain weight and low blood pressure in some patients who have tried to treat with
other medications. During high doses injection of IL-2 other side effects have been
reported including heart beats and chest pain [106,107].