<em>Feeder Free Expanded Primary and iPSC-derived NK cells Maintain Cytotoxic Function Against Patient Derived 3D Tumoroids</em> — ASN Events

Feeder Free Expanded Primary and iPSC-derived NK cells Maintain Cytotoxic Function Against Patient Derived 3D Tumoroids (#205)

Erica Heipertz 1 , Marcus Bunn 1 , Maja Preradovic 1 , Logan Wilson 1 , Colin Paul 1 , Chris Yankaskas 1 , Mark Kennedy 1 , Matt Dallas 1 , Navjot Kaur 1 , Jasmine Padilla 1
  1. Thermo Fisher Scientific, Frederick, MD, United States

Immunotherapy, particularly CAR-T cell therapy, has emerged as a potent treatment for hematological cancers. However, the cell and gene therapy industry face significant challenges, including safety issues, rising treatment costs, efficacy in solid tumors, and speed to clinical application. Natural killer (NK) cells, key immune cells of the innate immune system, respond to cells they recognize as "non-self," including cancerous cells. Unlike T cells, NK cells offer an anticancer response that is not dependent on antigens, making them a potential "off-the-shelf" allogeneic therapeutic product.

Effective scale-up expansion of primary or iPSC-derived NK cells is critical for the success of NK cell immunotherapies. Gibco™ CTS™ NK-Xpander™ Medium expands functional primary and iPSC-derived NK cells in a feeder-free system and is compatible with multiple scale-up systems, including G-rex® and HyPerforma™ stir tanks. While NK cell expansion varies by donor, qualified donors yield up to 12 billion peripheral blood NK cells within 2 to 3 weeks.

For effective immunotherapy, NK cells must maintain their functionality post-expansion. We tested the ability of expanded primary and iPSC-derived NK cells to kill patient-derived endometrial, breast cancer, and colorectal tumoroids generated using the OncoPro™ Tumoroid Culture Medium Kit. The expanded NK cells maintain functionality and can kill patient-derived 3D tumoroids in a dose- and donor-dependent manner in a co-culture assay. This showcases a functional assay with arguably more physiological relevance than standard K562 killing assays.

Currently, CTS NK-Xpander Medium is used by multiple clinical sites to manufacture NK cells for treating blood cancers, including acute myeloid leukemia and advanced lymphoma. CTS NK-Xpander, together with the OncoPro Tumoroid Culture Medium Kit, may provide the cell and gene therapy industry the tools to expand and screen for optimal immunotherapy treatment strategies by pairing robust preclinical tumor models with cell expansion solutions for NK cell therapy manufacturing.