Allogeneic NK Cell ("SMT-NK") in Combination With Pembrolizumab in Advanced Biliary Tract Cancer
Status:
Unknown status
Trial end date:
2021-06-02
Target enrollment:
Participant gender:
Summary
The term of biliary tract cancer (BTC) or cholangiocarcinoma refers to all tumors that arise
from the biliary tract or the biliary drainage system, including the gallbladder. According
to the data from National Cancer Information Center in 2016, annual incidence of the cancer
in Korea is 6,685 (13.1 per 100,000 population) which corresponds to about 2.9% of all
cancers.
BTC is one of the most prognostic cancer with less than 30% of 5-year survival rate and the
case with long-term survival can be possibly done with early detection of the cancer.
However, most of BTC is found in advanced stages due to the difficulty of early detection,
resulting in that the 5-year survival rate of the advanced BTC becomes less than 3%. More
than 50% of the patients depends on Gemcitabine based chemotherapy but response rate of the
chemotherapy remains around 30%. Thus, improving the survival rate with the standard
chemotherapy is very limited and furthermore selection of second-line therapy is not easy.
For this reason, development of an alternative therapeutic agent is urgently required.
NK (natural killer) cells are important cytotoxic innate immune cells that are involved in
the elimination of cancer cells. Two main NK cell subsets have been defined on the basis of
CD56 and CD16 expression: CD56^brightCD16- NK subset produces abundant cytokines including
interferon-γ (IFN-γ) and tumor necrosis factor-α, whereas CD56^dimCD16+ NK subpopulation has
high cytolytic activity and releases the granules containing perforin and granzymes.
Various clinical studies have been conducted to treat cancers using NK cells worldwide
including Korea and therapeutic clinical results are shown for various cancers. The clinical
application of NK cells is carried out by culturing and activating the NK cells isolated from
blood of either patient (autologous) or blood donor (allogeneic). Recently, NK cell therapy
for cholangiocarcinoma has been successfully done (NCT03358849) with allogeneic NK cell,
showing safety and potential efficacy.
Like T cells, a recent study with digestive cancer has shown that NK cells also express PD-1,
especially with more number of PD-1 in cancer patients than in healthy individuals,
suggesting that blocking PD-1 can be used as a potential strategy to increase the anticancer
activity of NK cells. Therefore, combined therapy with the immune-check point such as
pembrolizumab can be useful in elevating the anticancer activity of NK cells.