69P - NK-cell based delivery of anticancer therapeutics (69P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Renal Cell Cancer
Genitourinary Cancers
Surgical oncology
Radiation oncology
Presenter Olga Koval
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors O. Koval1, O. Volkova2, S. Kulemzin2, A. Gorchakov2, A. Tkachenko1, A. Nushtaeva1, E. Kuligina1, V. Richter1, A. Taranin2
  • 1Biotechnology, Institute of Chemical Biology and Fundamental Medicine SB RAS, 630090 - Novosibirsk/RU
  • 2Immunogenetics, Institute of Molecular and cellular Biology, Novosibirsk/RU



The promise of cancer immunotherapy has been translated into clinical success with the recent approval of adoptive cell transfer of T cells expressing chimeric antigen receptors (CARs) as a therapy for B cell malignancies. However, the progress of using CAR T cells in the context of solid cancers has been limited so far. We propose that use of “armored” CAR NK-cells secreting an anticancer peptide lactaptin may help deliver this agent in its highly active form into the tumor stroma thereby increasing its local concentration and boosting antitumor effects of the CAR.


We designed lentiviral constructs allowing stable transduction of human cell lines with cassettes encoding two secreted forms of lactaptin that differ in their leader sequences.


Lactaptin was successfully produced in HEK293T and YT cell lines. Its in vitro activity in the conditioned media was measured against a panel of sensitive cancer cells: MDA-MB-231 breast adenocarcinoma, PC3 prostate cancer and T98G glioblastoma. We evaluated that lactaptin from conditioned media showed greater than 50-fold increase in cytotoxicity compared to the recombinant lactaptin produced in E. coli.


This opens an opportunity to “armor” CAR YT cells with a cassette allowing secretion of lactaptin in situ, which in turn should improve the anticancer activity of adoptively transferred CAR YT cells. Experiments to test this approach in vitro and in vivo are underway.

Clinical trial identification

Legal entity responsible for the study

Institute of Chemical Biology and Fundamental Medicine


Russian Ministry of Education and Science, Agreement 14.604.21.0169 (unique project identifier RFMEFI60417X0169)


All authors have declared no conflicts of interest.