Intratumoral Injection of Allogeneic NK Cell With Chemotherapy in a Triple-negative Breast Cancer Preclinical Model.

Abstract

Background/aim: Conventional therapies for triple-negative breast cancer (TNBC) usually exhibit low efficacy. This study aimed to demonstrate the feasibility and antitumor efficacy of intratumoral (IT) injection of allogeneic natural killer (NK) cells with or without chemotherapy in the TNBC preclinical model.

Materials and methods: The TNBC preclinical models were generated in athymic nude and NOD/SCID mice. We assessed NK cell biodistribution and efficacy through bioimaging, immunohistochemistry, TUNEL assay and tumor growth pattern following peritumoral (PT), intravenous (IV) and IT injections. The in vitro anticancer effects of NK cells combined with chemotherapy (paclitaxel and carboplatin) were evaluated using MTS, qRT-PCR, and FACS analysis. In vivo anticancer effect was analyzed by tumor growth patterns and TUNEL assay.

Results: IT injection of NK cells resulted in superior tumor infiltration, apoptosis induction, and localized accumulation compared to PT and IV routes. Despite using only 10% of the NK cell dose used for IV administration, IT injection achieved comparable tumor growth suppression. Furthermore, combining IT NK cell therapy with chemotherapy produced additive effects, enhancing both tumor growth inhibition and apoptosis. Chemotherapy was found to upregulate the expression of NKG2D ligands at both mRNA and protein levels on cancer cells, potentially increasing their susceptibility to NK cell-mediated cytotoxicity.

Conclusion: IT injection of NK cells was feasible and added anticancer efficacy to systemic chemotherapy in TNBC preclinical models. Therefore, this study supports the rationale of further clinical development of IT NK therapy with or without chemotherapy in patients with TNBC.