Supercharged NK Cell-Based Immuotherapy in Humanized Bone Marrow Liver and Thymus (Hu-BLT) Mice Model of Oral, Pancreatic, Glioblastoma, Hepatic, Melanoma and Ovarian Cancers

Abstract

In this paper, we review a number of <i>in vitro</i> and <i>in vivo</i> studies regarding the efficacy of supercharged NK (sNK) cell therapy in elimination or treatment of cancer. We have performed studies using six different types of cancer models of oral, pancreatic, glioblastoma, melanoma, hepatic and ovarian cancers using hu-BLT mice. Our <i>in vitro</i> studies demonstrated that primary NK cells preferentially target cancer stem-like cells (CSCs)/poorly differentiated tumors whereas sNK cells target both CSCs/poorly-differentiated and well-differentiated tumors significantly higher than primary activated NK cells. Our <i>in vivo</i> studies in humanized-BLT mice showed that sNK cells alone or in combination with other cancer therapeutics prevented tumor growth and metastasis. In addition, sNK cells were able to increase IFN-<i>γ</i> secretion and cytotoxic function by the immune cells in bone marrow, spleen, gingiva, pancreas and peripheral blood. Furthermore, sNK cells were able to increase the expansion and function of CD8+ T cells both in <i>in vitro</i> and <i>in vivo </i>studies. Overall, our studies demonstrated that sNK cells alone or in combination with other cancer therapeutics were not only effective against eliminating aggressive cancers, but were also able to increase the expansion and function of CD8+ T cells to further target cancer cells, providing a successful approach to eradicate and cure cancer.

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

“…The resulting Hu-BLT mouse models are well-suited for research on tumor immunotherapy ( Chuprin et al, 2023 ; De La Rochere et al, 2018 ). In addition to T cells, Hu-BLT mouse models can be used to study cancer-related NK cells, which are part of the innate immune system ( Chuprin et al, 2023 ; Kaur & Jewett, 2023 ). Notably, studies using Hu-BLT mouse models have demonstrated that human NK cells exhibit anti-tumor activity against poorly differentiated human oral squamous cells ( Kaur & Jewett, 2023 ; Kaur et al, 2018 ).…”