239- ARH460-22-1 has cytotoxic activity in vitro against human breast cancer, colon
cancer and melanoma cell lines. Ongoing research is aimed at identifying and
validating the antibody target, and showing antibody safety and specifi city.
A humanized version of this antibody is currently under development.
The long-term aim of targeted antibody therapy is to match multiple antibodies
to different antigens on each patient’s cancer cell, delivering multiple cancer killing
messages simultaneously. Personalized therapy will improve on targeted therapy by
further reducing the risks of failed treatment and improving the likelihood of cure.
Genentech’s anticancer drug Herceptin may be considered the fi rst targeted anti-
body therapy in that it is only appropriate for use in patients who over-express the
Her2-Neu antigen on the surface of their breast cancer cells.
Immunotherapy of Dormant Cancer
Clinical cancer dormancy is evident from the detection of circulating tumor cells
(CTCs) in the blood and tissue-residing disseminated tumor cells in the bone mar-
row of cancer survivors who have been clinically disease free. Emerging evidence
from clinical and preclinical studies suggests that tumor dormancy is a critical step
in the development of both primary cancer and advanced-stage disease. A review
has shown that (i) naturally occurring tumor dormancy precedes occurrence of pri-
mary cancer; and (ii) conventional cancer therapies result in treatment-induced
tumor dormancy, which in turn could lead to distant recurrence of cancer or perma-
nent tumor dormancy, depending on immunogenic status of dormancy (Manjili
2014 ). Given that cellular dormancy is an evolutionary conserved survival mecha-
nism in biologic systems, any stress or cytotoxic therapy could trigger cellular dor-
mancy. Therefore, a successful cancer therapy is likely to be achieved by establishing
permanent tumor dormancy and preventing distant recurrence of cancer or by elimi-
nating dormant tumor cells. This could be accomplished by cancer immunotherapy
because of the establishment of long-term memory responses.
Mechanisms involved in metastatic cancer dormancy − cellular dormancy, angio-
genic dormancy, and immune-mediated dormancy − can restrain disseminated cancer
cells, thereby promoting their permanent dormancy (Romero et al. 2014 ). CD8+ T
lymphocytes play a relevant role in maintaining immune equilibrium with metastatic
dormant cells, and MHC class I surface expression on tumor cells may also be
involved. NK cells have an activator function that triggers a CTL response. Furthermore,
immune dormancy promotes cancer cell growth arrest and angiogenic control.
Immunotherapeutic interventions in metastatic dormancy may help to control or
eradicate cancer. Activation or increase of the CTL immune response or reversal of
cancer cell-induced CTL immunosuppression might be useful for restraining or
destroying metastatic cells. These objectives may be achieved by recovering or
increasing MHC class I surface expression on cancer cells or by activating NK cells.
Thus immune-mediated metastasis dormancy provides an opportunity for targeting
cancer by immunotherapy.
Immunotherapy of Cancer