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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Yano, Hiroshi Thakur, Archana Tomaszewski, Elyse N Choi, Minsig Deol, Abhinav Lum, Lawrence G |
| Abstract | Background Ipilimumab is an antagonistic monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) that enhances antitumor immunity by inhibiting immunosuppressive activity of regulatory T cells (Treg). In this study, we investigated whether inhibiting Treg activity with ipilimumab during ex vivo T cell expansion could augment anti-CD3-driven T cell proliferation and enhance bispecific antibody (BiAb)-redirected antitumor cytotoxicity of activated T cells (ATC). Methods PBMC from healthy individuals were stimulated with anti-CD3 monoclonal antibody with or without ipilimumab and expanded for 10-14 days. ATC were harvested and armed with anti-CD3 x anti-EGFR BiAb (EGFRBi) or anti-CD3 x anti-CD20 BiAb (CD20Bi) to test for redirected cytotoxicity against COLO356/FG pancreatic cancer cell line or Burkitt’s lymphoma cell line (Daudi). Results In PBMC from healthy individuals, the addition of ipilimumab at the initiation of culture significantly enhanced T cell proliferation (p = 0.0029). ATC grown in the presence of ipilimumab showed significantly increased mean tumor-specific cytotoxicity at effector:target (E:T) ratio of 25:1 directed at COLO356/FG and Daudi by 37.71% (p < 0.0004) and 27.5% (p < 0.0004), respectively, and increased the secretion of chemokines (CCL2, CCL3, CCL4,CCL5, CXCL9, and granulocyte-macrophage colony stimulating factor(GM-CSF)) and cytokines (IFN-γ, IL-2R, IL-12, and IL-13), while reducing IL-10 secretion. Conclusions Expansion of ATC in the presence of ipilimumab significantly improves not only the T cell proliferation but it also enhances cytokine secretion and the specific cytotoxicity of T cells armed with bispecific antibodies. |
| Related Links | https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/1479-5876-12-191.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14795876 |
| DOI | 10.1186/1479-5876-12-191 |
| Journal | Journal of Translational Medicine |
| Issue Number | 1 |
| Volume Number | 12 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-07-09 |
| Access Restriction | Open |
| Subject Keyword | Biomedicine Medicine Public Health Ipilimumab Cytotoxic T-lymphocyte antigen-4 (CTLA-4) Bispecific antibody Pancreatic cancer Colorectal cancer Burkitt’s lymphoma Activated T cells Immunotherapy Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology Medicine |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 6.3/2023 |
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