In cancer patients, a certain number of cytotoxic T lymphocytes (CTLs)
specific for cancer antigen are formed; however, most of these CTLs remain inactive
due to various suppressive mechanisms such as improper DC activation (anergy
induction) or suppression by regulatory T cells. The conventional strategies have been
directed to expand the remaining CTLs in vitro or in vivo, to diverge the anergic T cells
to an activated status, or to inhibit regulatory T cells. Although the resulting activated
CTLs exhibit certain activity in killing tumor cells, in most cases the activity of CTLs is
not sufficient enough to result in cure of the patient. One of the major limiting factors in
this type of approach is the short life span of activated CTLs. Currently we are trying to
overcome this problem by utilizing the iPSC (induced pluripotent stem cell) technology.
The concept of our strategy is that it is possible to obtain de novo generated tumor
antigen specific CTLs almost unlimitedly when one firstly produces iPSCs from tumor
antigen specific CTLs and subsequently regenerate CTLs from such iPSCs. In line with
this concept, we have succeeded in establishing iPSCs from mature CTLs specific for
the melanoma antigen MART-1, and in regenerating MART-1 specific T cells from
such iPSCs. This approach may provide a breakthrough in the future in the tumor
immunotherapy.
Keywords: Cloning, cytotoxic T lymphocytes (CTLs), induced pluripotent stem
cells (iPSCs), MART-1, melanoma, reprogramming.
