| Autor: |
Thakur, Archana, Norkina, Oxana, Lum, Lawrence |
| Předmět: |
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| Zdroj: |
Cancer Immunology, Immunotherapy; Dec2011, Vol. 60 Issue 12, p1707-1720, 14p |
| Abstrakt: |
In this study, we developed a unique in vitro model to mimic the endogenous tumor microenvironment to understand the effect of immunotherapy with activated T-cells (ATC) armed with anti-CD3 × anti-Her2 bispecific antibody (aATC) on antibody response by naive immune cells. This model contained a co-culture of naïve peripheral blood mononuclear cells (PBMC), breast cancer cells (SK-BR-3), ATC or aATC and CpG ODNs. Culture supernatants were tested at various time points for anti-SK-BR-3 antibodies by ELISA, Western blot and flow cytometry. PBMC cocultured with non-irradiated aATC or irradiated (*) aATC showed significant increases in anti-tumor antibody production at day 14 ( P < 0.0001) in the presence of CpG-ODN compared to unstimulated PBMC cultures ( n = 9). Antibody specificity was confirmed by ELISA, Western blot and flow cytometry. Co-cultures containing *aATC and CpG showed significantly enhanced levels of IgG ( P < 0.001) and cytokines that promote IgG synthesis including IL-13 ( P < 0.02), IFNγ ( P < 0.01) and GM-CSF ( P < 0.05) compared to unstimulated PBMC control ( n = 3). We show that aATC targeting and lysis of tumor cells induces an anti-tumor antibody response in our in vitro model. This model provides a unique opportunity to evaluate the interactions of T-cells, B-cells, and antigen-presenting cells leading to specific anti-tumor antibody responses. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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