Immunological Responses against HER2-targeted Idarubicin-ZHER2 Conjugate in BALB/c Mice

• Published in: Iranian journal of allergy, asthma, and immunology Vol. 18; no. 5; p. 501
• Main Authors: Siavoshinia, Leila, Jamalan, Mostafa, Zeinali, Majid, Mohammadzadeh, Ghorban
• Format: Journal Article
• Language: English
• Published: Iran Tehran University of Medical Sciences 23.10.2019
• Subjects: Animals; Cell lines; Chemotherapy; Cytokine; Cytokines; Dose dependency; Drug development; Epidermal growth factor; ErbB-2 protein; Female; Human epidermal growth factor receptor 2; Idarubicin - immunology; Idarubicin-ZHER2 affibody conjugate; Immune response; Immune response (cell-mediated); Immune response (humoral); Immunity, Cellular - immunology; Immunity, Humoral - immunology; Immunoconjugates; Immunoglobulin G; Immunoglobulin G - immunology; Inflammation; Inflammation - immunology; Interferon-gamma - immunology; Interleukin 10; Interleukin-10 - immunology; Mice; Mice, Inbred BALB C; Receptor, ErbB-2 - immunology; Rodents; Splenocytes; γ-Interferon; Idarubicin-ZHER2 affibody conjugate; Immune response; Human epidermal growth factor receptor 2; Immunoglobulin G; Cytokine
• ISSN: 1735-1502; 1735-5249
• DOI: 10.18502/ijaai.v18I5.1919

Targeting of cancerous cells with a high level of human epidermal growth factor receptor 2 (HER2) expressions by drug immunoconjugates is a new approach for specific delivery of chemotherapeutic agents. Our previous work indicated that idarubicin-ZHER2 affibody conjugate has a great potential for the treatment of HER2-overexpressing malignant cell lines but possible induced immune response against constructed conjugate was not addressed. In the current study, the possibility of induction of humoral and cellular immune responses against idarubicin-ZHER2 affibody conjugate in BALB/c mice was investigated. For assessment of the induced immune response, prepared and qualified idarubicin-ZHER2 affibody conjugate was administrated intravenously to BALB/c mice and the induced cellular immune response was evaluated by measuring secretion levels of interferon gamma (IFN-γ) and interleukin 10 (IL-10) cytokines by the splenocytes. Humoral response of treated mice was also assessed by measuring total immunoglobulin G (IgG) titer in mice sera. The obtained results showed that idarubicin-ZHER2 affibody conjugate at any examined concentrations could not induce secretion of IFN-γ as a pro-inflammatory cytokine. A mild increase in the level of regulatory IL-10 cytokine was seen in the treated mice although no dose dependency in the level of IL-10 production was observed. Furthermore, results showed that idarubicin-ZHER2 conjugate could not induce IgG production in the treated mice. Based on these findings, the idarubicin-ZHER2 conjugate can be considered as a candidate for the development of new therapeutics against HER2-overexpressing cancers although further in vivo studies are needed.