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In vitro synthesis of primary specific anti-breast cancer antibodies by normal human peripheral blood mononuclear cells.
- Source :
-
Cancer Immunology, Immunotherapy . Dec2011, Vol. 60 Issue 12, p1707-1720. 14p. - Publication Year :
- 2011
-
Abstract
- 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]
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 60
- Issue :
- 12
- Database :
- Academic Search Index
- Journal :
- Cancer Immunology, Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 67316704
- Full Text :
- https://doi.org/10.1007/s00262-011-1056-9