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1.
BMC Cancer ; 24(1): 339, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486205

RESUMO

BACKGROUND: Beta-(1,3)(1,6)-D-glucan is a complex polysaccharide, which is found in the cell wall of various fungi, yeasts, bacteria, algae, barley, and oats and has immunomodulatory, anticancer and antiviral effects. In the present study, we investigated the effect of beta-(1,3)(1,6)-D-glucan derived from yeast on the proliferation of primary NK cells and breast cancer cell lines in 2D and 3D models, and on the cytotoxicity of primary NK cells against breast cancer cell lines in 2D and 3D models. METHODS: In this study, we investigated the effects of different concentrations of yeast-derived beta-(1→3)(1→6)-D-glucan on the proliferation and cytotoxicity of human NK cells and breast cancer cell lines in 2D and 3D models using the XTT cell proliferation assay and the CellTiter-Glo® 2.0 assay to determine the cytotoxicity of human NK cells on breast cancer cell lines in 2D and 3D models. RESULTS: We found that the co-incubation of NK cells with beta-glucan in the absence of IL2 at 48 h significantly increased the proliferation of NK cells, whereas the co-incubation of NK cells with beta-glucan in the presence of IL2 (70 U/ml) increased the proliferation of NK cells but not significantly. Moreover, beta-glucan significantly inhibited the proliferation of breast cancer cell lines in 2D model and induced a weak, non-significant growth inhibitory effect on breast cancer multicellular tumor spheroids (3D). In addition, the cytotoxicity of NK cells against breast cancer cell lines was examined in 2D and 3D models, and beta-glucan significantly increased the cytotoxicity of NK cells against MCF-7 (in 2D). CONCLUSIONS: Yeast derived beta-(1,3)(1,6)-D-glucan could contribute to the treatment of cancer by enhancing NK cell immune response as well as contributing to inhibition of breast cancer cell growth.


Assuntos
Neoplasias da Mama , beta-Glucanas , Humanos , Feminino , Células MCF-7 , Glucanos/farmacologia , Neoplasias da Mama/patologia , Saccharomyces cerevisiae , Interleucina-2 , Células Matadoras Naturais , beta-Glucanas/farmacologia
2.
Int J Mol Sci ; 24(10)2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37240385

RESUMO

There is a medical need to develop new and effective therapies against triple-negative breast cancer (TNBC). Chimeric antigen receptor (CAR) natural killer (NK) cells are a promising alternative to CAR-T cell therapy for cancer. A search for a suitable target in TNBC identified CD44v6, an adhesion molecule expressed in lymphomas, leukemias and solid tumors that is implicated in tumorigenesis and metastases. We have developed a next-generation CAR targeting CD44v6 that incorporates IL-15 superagonist and checkpoint inhibitor molecules. We could show that CD44v6 CAR-NK cells demonstrated effective cytotoxicity against TNBC in 3D spheroid models. The IL-15 superagonist was specifically released upon recognition of CD44v6 on TNBC and contributed to the cytotoxic attack. PD1 ligands are upregulated in TNBC and contribute to the immunosuppressive tumor microenvironment (TME). Competitive inhibition of PD1 neutralized inhibition by PD1 ligands expressed on TNBC. In total, CD44v6 CAR-NK cells are resistant to TME immunosuppression and offer a new therapeutic option for the treatment of BC, including TNBC.


Assuntos
Receptores de Antígenos Quiméricos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Interleucina-15/metabolismo , Ligantes , Linhagem Celular Tumoral , Células Matadoras Naturais , Imunoterapia Adotiva , Microambiente Tumoral
3.
Cancers (Basel) ; 16(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38254876

RESUMO

Colorectal carcinoma (CRC) presents a formidable medical challenge, demanding innovative therapeutic strategies. Chimeric antigen receptor (CAR) natural killer (NK) cell therapy has emerged as a promising alternative to CAR T-cell therapy for cancer. A suitable tumor antigen target on CRC is carcinoembryonic antigen (CEA), given its widespread expression and role in tumorigenesis and metastasis. CEA is known to be prolifically shed from tumor cells in a soluble form, thus hindering CAR recognition of tumors and migration through the TME. We have developed a next-generation CAR construct exclusively targeting cell-associated CEA, incorporating a PD1-checkpoint inhibitor and a CCR4 chemokine receptor to enhance homing and infiltration of the CAR-NK-92 cell line through the TME, and which does not induce fratricidal killing of CAR-NK-92-cells. To evaluate this therapeutic approach, we harnessed intricate 3D multicellular tumor spheroid models (MCTS), which emulate key elements of the TME. Our results demonstrate the effective cytotoxicity of CEA-CAR-NK-92 cells against CRC in colorectal cell lines and MCTS models. Importantly, minimal off-target activity against non-cancerous cell lines underscores the precision of this therapy. Furthermore, the integration of the CCR4 migration receptor augments homing by recognizing target ligands, CCL17 and CCL22. Notably, our CAR design results in no significant trogocytosis-induced fratricide. In summary, the proposed CEA-targeting CAR-NK cell therapy could offer a promising solution for CRC treatment, combining precision and efficacy in a tailored approach.

4.
J Microbiol Immunol Infect ; 43(2): 147-54, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20457432

RESUMO

BACKGROUND/PURPOSE: Mixed infections caused by different Candida species are the rule rather than the exception. The discrimination between the two closely related species Candida albicans and Candida dubliniensis is not trivial. Therefore, there is a need for fast, reliable, and inexpensive methods with high specificity for the identification and differentiation of these two Candida species, which are frequently detected in the oral cavities of patients with a human immunodeficiency virus infection. METHODS: We applied several phenotypic identification methods (growth on Rice-agar, Bird-seed agar, CHROMagar Candida, API ID 32C; growth at 42 degrees C and 45 degrees C) and compared them with genotyping by arbitrarily primed-polymerase chain reaction. RESULTS: A sensitivity of 44% for the identification of C. dubliniensis was achieved for growth on Rice-agar, 97% for discrimination on Bird-seed agar, 95% with the assimilation profile index API ID 32C, and 97% when grown at 45 degrees C. We found two API codes not described for C. dubliniensis so far. Additionally, 88% of our C. dubliniensis isolates assimilated palatinose, in contrast to the 1% described in the API reference manual. CONCLUSION: According to our results, cultivation of Candida isolates on Bird-seed agar after screening on CHROMagar Candida is a very sensitive, simple, and cost-effective method for discriminating C. dubliniensis from C. albicans in routine practice.


Assuntos
Candida/classificação , Candida/isolamento & purificação , Candidíase/diagnóstico , Candidíase/microbiologia , Candida/genética , Candida/fisiologia , Impressões Digitais de DNA , Genótipo , Humanos , Técnicas de Tipagem Micológica/métodos , Fenótipo , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade
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