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cells, gamma delta T (gdT), and immune checkpoint inhibitors in the form of mAbs are currently still under
active investigation (see “Future perspectives” below).

Adoptive cell-based therapy
[10]
A variety of effector cells including NK , lymphokine-activated killer (LAK) [11,12] , cytokine-induced killer
[15]
[14]
[13]
(CIK) , tumor-infiltrating lymphocyte (TIL) , dendritic cell (DC) and antigenic peptide pulsed-
[16]
[17]
DC expanded cytotoxic tlymphocyte (CTL) , and gdT cells have been used as part of adoptive cell-
based immunotherapies for different human cancer types, with varying degrees of efficacies obtained in
the past. Most important developments in the cell-based immunotherapy in recent years include (1) the
rapid expansion methods for NK and TILs using stimulatory or feeder cells transfected with the genes of
continuous 4-1BB co-stimulatory signals [18,19] ; and (2) the development of engineered T cell receptor (TCR)-T
[21]
[20]
cells and CAR-T cells , modes of T cell adoptive cell immunotherapy with impressive clinical results that
had not been achieved previously. Apart from its ease for expansion, potent killing effect and requirement of
only one in vivo administration, another advantage of CAR-T therapy is independent of TCR recognition.
In other words, its tumor killing should be effective for patients in whom the surface HLA-class I expression
[24]
on cancer cells was deficient or lost [22,23] , or whose tumors were drug-resistant , as long as the patient’s
tumor cells could all be detected by the CAR-T cells to be infused [24,25] . It is well known that the expression of
HLA class I in cancer cells of patients with the advanced stage or under the influence of treatment tends to
become deficient or lost totally [22,23,26] , one way for tumor cells to escape from the host immune surveillance.
Of note, these modes of adoptive cell transfer are considered personalized immunotherapies, as patients’ own
immune cells are processed, expanded, and infused back to the individual patients.

Monoclonal antibodies
The discovery of hybridoma technology in the 1970s for the production mAbs was another major technical
[27]
advance . The limitation of the use of polyclonal antibodies have been the inability to generate reproducible,
high-titer, specific antibodies, and to precisely define the antigenic molecules identified with such polyclonal
antibodies. The development of mAbs each with its fine specificity has largely circumvented the problems
associated with polyclonal antibodies, allowing an alternative way, other than molecular cloning, to produce
a variety of biologicals of therapeutic grade. Furthermore, processes to be able to “chimerize” or “humanize”
murine mAbs have produced therapeutic antibodies to be used in the clinical treatment of cancer and
autoimmune patients possible with low immunogenicity. mAbs are highly specific for the antigens on
the tumor cells and immune cells. In addition, these mAbs and genetic sequencing testing allow for the
individual tailoring of treatment to each patient, now known as “precision medicine”. To be specific for
cancer patients, such tailoring is called “precision oncology”.

FUTURE PERSPECTIVES
There is no doubt that we now have more powerful tools and technologies for improving cancer therapy.
Cancer biotherapy provides additional approaches which may work effectively in combination with surgery,
radiation, targeted therapy or chemotherapy. It may work effectively through mAbs in directing radioisotopes
selectively to the tumor cells and with chemotherapy, and other cytostatic and cytotoxic molecules as
immunoconjugates in directing those molecules to the tumor bed, enhancing selectivity and biological
activity. It may also work more effectively through a combination treatment of both innate and adaptive
cellular therapy as compared with single cell therapy alone [28,29] . Thus, biotherapy offers the great hope to
cancer patients for selective treatment to enhance therapeutic/toxic ratio and at the same time lessen the
problem of nonspecific toxicity, a major impediment to the development of more effective cancer treatment.

The coming decade will have many opportunities to pursue new approaches in cancer treatment. Basic
scientists and physician/scientists requiring special training and expertise will use new techniques in the
laboratory and clinic. Currently, the medical oncologist trained in the administration of chemotherapy drugs
is not well prepared to administer biological substances for cancer treatment. Biotherapy uses biological