Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model

Abstract

Introduction: Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model. Methods: Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3. Results: The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data. Conclusion: Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

Contribution of natural killer cells in innate immunity against colorectal cancer

“…Our research group demonstrated that pretreated checkpoint blockade NK cells could effectively enhance the NK cells’ trafficking in TME and beneficially reduce the tumor cell mitosis in gastric cancer xenograft model ( 189 ). However the same results was not achieved in chemo immune cell therapy of Intratumoral injection of NK cells in combination with capecitabine in gastric cancer xenograft model in the other study of our group ( 190 ).…”

Development and implementation of natural killer cell simultaneous ADCC and direct killing assay

“…Samples were then blocked with 5 μL human FcX block (cat#422302; 10 min). Following this, samples were stained (15 min) with the following flow cytometry antibodies: a lineage cocktail (anti-CD3, anti-CD14, anti-CD19), anti-CD16, and anti-CD56 ( Table 1 ) [ 10 , [17] , [18] , [19] , [20] , [21] ]. PBS was added to sample tubes for a final volume of 3 mL.…”

A Case Report of Pathologically Complete Response of a Huge Lymph Node Metastasis of Colorectal Cancer After Treatment with Intratumoral Oncolytic Virus H101 and Capecitabine

“… 6 Capecitabine, the first-line chemotherapeutic agent for CRC, has been shown to change the tumour microenvironment into an “immune-hot” subtype in patients, improve the antitumor effect of NK cells, and reduce myeloid-derived suppressor cells (MDSCs) ( Figure 1 ). 7 , 8

Figure 1 Augmentation of Immune Response through Oncolytic Viruses and Capecitabine Co-Therapy.

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