Bispecific antibodies enhance tumor‐infiltrating T cell cytotoxicity against autologous HER‐2‐expressing high‐grade ovarian tumors

Autor: Dieter Kabelitz, Daniela Wesch, Matthias Peipp, Jörg Weimer, Dirk Bauerschlag, Lisa Janitschke, Vjola Sulaj, Norbert Arnold, Nina Hedemann, Daniel Gonnermann, Hans-Heinrich Oberg
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cytotoxicity
Immunologic
CD3 Complex
Receptor
ErbB-2
Receptors
Antigen
T-Cell
alpha-beta
cisplatin
Gene Expression
Carcinoma
Ovarian Epithelial
0302 clinical medicine
Antineoplastic Agents
Immunological
Ovarian carcinoma
Antibodies
Bispecific
Immunology and Allergy
Guest Editors: Sarina Ravens and Immo Prinz
Receiving and Translating Signals via the Gamma Delta T cell Receptor
Ovarian Neoplasms
Ascites
Receptors
Antigen
T-Cell
gamma-delta
Articles
Middle Aged
Tumor antigen
bispecific antibody
medicine.anatomical_structure
ovarian cancer
030220 oncology & carcinogenesis
Female
Adult
human γδ T cells
T cell
CD3
Immunology
Primary Cell Culture
Biology
Article
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
medicine
Humans
Lymphocyte Count
T-cell receptor
HER‐2
Cell Biology
medicine.disease
Coculture Techniques
030104 developmental biology
Cancer research
biology.protein
Neoplasm Grading
Ovarian cancer
T cell subsets
CD8
Ex vivo
T-Lymphocytes
Cytotoxic
Zdroj: Journal of Leukocyte Biology
ISSN: 1938-3673
0741-5400
Popis: Epithelial ovarian cancer displays the highest mortality of all gynecological tumors. A relapse of the disease even after successful surgical treatment is a significant problem. Resistance against the current platinum‐based chemotherapeutic standard regime requires a detailed ex vivo immune profiling of tumor‐infiltrating cells and the development of new therapeutic strategies. In this study, we phenotypically and functionally characterize tumor cells and autologous tumor‐derived αβ and γδ T lymphocyte subsets. Tumor‐infiltrating (TIL) and tumor‐ascites lymphocytes (TAL) were ex vivo isolated out of tumor tissue and ascites, respectively, from high‐grade ovarian carcinoma patients (FIGO‐stage IIIa‐IV). We observed an increased γδ T cell percentage in ascites compared to tumor‐tissue and blood of these patients, whereas CD8+ αβ T cells were increased within TAL and TIL. The number of Vδ1 and non‐Vδ1/Vδ2‐expressing γδ T cells was increased in the ascites and in the tumor tissue compared to the blood of the same donors. Commonly in PBL, the Vγ9 chain of the γδ T cell receptor is usually associated exclusively with the Vδ2 chain. Interestingly, we detected Vδ1 and non‐Vδ1/Vδ2 T cells co‐expressing Vγ9, which is so far not described for TAL and TIL. Importantly, our data demonstrated an expression of human epidermal growth factor receptor (HER)‐2 on high‐grade ovarian tumors, which can serve as an efficient tumor antigen to target CD3 TIL or selectively Vγ9‐expressing γδ T cells by bispecific antibodies (bsAbs) to ovarian cancer cells. Our bsAbs efficiently enhance cytotoxicity of TIL and TAL against autologous HER‐2‐expressing ovarian cells.
Tumor‐infiltrating γδ T cells are attractive effector cells for targeting with bispecific antibodies in the treatment of ovarian cancer cells.
Databáze: OpenAIRE
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