iPSC-Derived NK Cells and Anti-PD-1 Antibody Synergize to Enhance T Cell Cytokine and Cytolytic Responses Against Multiple Tumors

The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors (CIR), such as programmed death 1 (PD-1), has transformed the oncology landscape. However, many tumor subtypes are resistant to CIR-targeted therapy, and relapse remains a significant concern. Therefore, combination of novel immunotherapies with CIR targeting remains a promising and widely investigated approach to bolster anti-tumor responses and to overcome tumor resistance to CIR therapy.Natural killer (NK) cells mediate direct tumor cell lysis and are key regulators of T cell responses through the production of inflammatory cytokines and chemokines. In many cancers, NK cell numbers are low and their functional responses are sub-optimal. The use of allogeneic NK cell immunotherapy has shown significant clinical promise for the treatment of acute myelogenous leukemia (AML). However, this approach has inherent limitations with respect to the number of NK cells that can be isolated and variability in the quantity and quality of NK cells between donors. To overcome these barriers, we have developed a system for large scale expansion of NK cells derived from induced pluripotent stem cells (iPSCs) to be combined with CIR antibodies for multiple tumor types (Figure 1A). iPSC derive NK (iNK) cells (defined as CD45+CD3-CD56+) differentiated with high efficiency in this culture system (Figure 1B), and overall expansion from the hematopoietic progenitor stage to end of the protocol was...
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: Pre-clinical T and NK Cell Immunotherapies Source Type: research