Paulina Nowakowska's research while affiliated with Goethe-Universität Frankfurt am Main and other places

Publications (10)

Article
Full-text available
The ABO blood group system is the most important factor in clinical transfusion medicine and is implicated in a number of human diseases. ABO antigens are not confined to red blood cells (RBCs) and are widely expressed in a variety of human cells and tissues. To date, many alleles with variant ABO expression have been identified and in many cases t...
Article
Full-text available
Background: The NK-92/5.28.z cell line (also referred to as HER2.taNK) represents a stable, lentiviral-transduced clone of ErbB2 (HER2)-specific, second-generation CAR-expressing derivative of clinically applicable NK-92 cells. This study addresses manufacturing-related issues and aimed to develop a GMP-compliant protocol for the generation of NK-...
Article
Full-text available
Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however...
Article
Full-text available
Natural killer (NK) cells have been used in several clinical trials as adaptive immunotherapy. The low numbers of these cells in peripheral blood mononuclear cells (PBMC) have resulted in various approaches to preferentially expand primary NK cells from PBMC. While some clinical trials have used the addition of interleukin 2 (IL-2) to co-stimulate...
Article
In clinical transfusion and transplantation medicine, AB0 is the most important blood group system. A and B antigens are synthesized by glycosyltransferases A and B encoded by co-dominantly inherited A and B genes. The 0 phenotype derives from a single nucleotide deletion; the resulting stop codon in the exon 7 of glycosyltransferase A leads to a l...
Article
Full-text available
Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expand...
Article
While EGFRvIII appears a logical target for immunotherapy, only a subpopulation of tumor cells express EGFRvIII and immune escape has been demonstrated. ErbB2 is overexpressed in a substantial proportion of glioblastomas and has been successfully utilized in immunotherapies. Natural killer (NK) cells are the first line of defense against viral infe...
Article
Full-text available
Poster presentation: 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC) Significant progress has been made over the last decade towards realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells, and have the intrinsic potential to extra...

Citations

... Table 2 and Figure 4, miR-1908 not only plays an important role in the pathogenesis of cancer but is also associated with the risk of four non-cancer diseases, including organ and tissue fibrosis (1, 7, 32), bipolar disorder (BD) (39, 40), Alzheimer's disease (AD) (15), RA (19). At the same time, miR-1908 is also involved in the regulation of lipid metabolites (51) and ABH antigen (52). ...
... Numerous approaches have been established to expand the targeting and effectiveness of NK cell cytotoxicity against tumor cells using genetic alteration techniques. Strategies employed to generate chimeric antigen receptor-NK (CAR-NK) cells have also been applied that not only increase the efficacy of NK cell therapy but also largely escalate the specificity of NK cell therapy (137,138). CARs are comprised of a singlechain extracellular variable fragment (scFv) and an intracellular immune cell activation domain (139,140). Using CAR-T as a prototype model, preliminary studies on NK cells integrated the 4-1BB co-stimulatory domain, which confers greater persistence; however, 2B4 is an NK cell-specific co-stimulatory domain that improves cell function in a number of ways, including increased cytotoxicity, persistence, proliferation, and cytokine secretion (141). ...
... Coexpansion of NK cells alongside γδ T cells is also logical considering the role of IL-2 in ex vivo expansion protocols used to specifically enrich and expand NK cells. 36 Notably, across all expansions, only those from 4/16 donors reached a threshold of >50% NK cells, suggesting that donor PBMCs more commonly yield γδ T cell-dominant expansions with our serumfree expansion protocol using zoledronate and IL-2, which also tend to yield higher overall cellular content. Ou et al.'s recent work corroborates this finding, demonstrating that of 43 healthy donors expanded using zoledronate and IL-2, approximately 70% of expansions produced a cellular product with >50% γδ T cell content. ...
... However, because this cell line is derived from a 50-year-old white male diagnosed with rapidly progressive non-Hodgkin's lymphoma, NK92 cells have to be lethally irradiated before infusion back to the patient, which tends to limit the in vivo persistence of the engineered cells and impair durable clinical efficacy. 40,41 This obstacle has been partially tackled via the expression of a high-affinity CD16 variant (haNK) to boost the effector function. 42 The clinical efficacy of this novel approach, along with the combined use of cancer vaccines or other agents, is yet to be revealed by ongoing clinical trials (NCT03387085, NCT03853317, NCT03387111, and NCT03586869). ...
... Previous studies of CAR-expressing NK92 cells showed a higher degree of tumor-infiltration by CAR-NK92 cells compared to unmodified counterpart in orthotopic xenograft models. 35,36 Third, irradiated NK111-αEpCAM-CAR seemed to persist for a certain period in vivo to allow adequate conversion of 5-FC to 5-FU and its diffusional export to take place. According to a previous study, the bystander effects can fail by inadequate 5-FC uptake, limited 5-FU export or rapid elimination of CD-expressing cells prior to sufficient 5-FU release. ...
... Previous pre-clinical studies have redirected CARmodified primary human NK cells against CD19 [26,27], CD20 [28], CD244 [29], and HER2 [30], and anti-CD19 CAR-modified donor-derived and haploidentical NK cells have successfully entered clinical trials for B-cell acute lymphoblastic leukemia (NCT00995137 and NCT01974479). Additionally, NK-92, a human NK cell line, has been used in a variety of clinical studies for solid tumor and hematologic malignancies [31,32], and also in pre-clinical CAR applications [33][34][35][36][37][38][39], and is therefore not only a good model for clonal NK cells, but also for autologous or allogeneic NK cell immunotherapy. ...