Abstract
Therapeutic vaccination with replication deficient adenovirus expressing a viral antigen linked to invariant chain was recently found to markedly delay the growth of B16.F10 melanomas expressing the same antigen; however, complete regression of the tumors was never observed. Here we show that the delay in tumor growth can be converted to complete regression and long-term survival in 30-40% of the mice by a booster vaccination plus combinational treatment with agonistic anti-CD40 monoclonal antibodies (mAb) and anti-CTLA-4 mAb. Regarding the mechanism underlying the improved clinical effect, analysis of the tumor-specific response revealed a significantly prolonged tumor-specific CD8 T cell response in spleens of the mice receiving the combinational treatment compared with mice receiving either treatment individually. Matching this, CD8 T cell depletion completely prevented tumor control.These results indicate that even with a strong tumor vaccine candidate, combinatorial treatment may be required to obtain clinically relevant results.
| Original language | English |
|---|---|
| Journal | Vaccine |
| Volume | 28 |
| Issue number | 41 |
| Pages (from-to) | 6757-64 |
| Number of pages | 8 |
| ISSN | 0264-410X |
| DOIs | |
| Publication status | Published - 24 Sept 2010 |
Keywords
- Adenoviridae
- Animals
- Antibodies, Monoclonal
- Antigens, CD
- Antigens, CD40
- Antigens, Differentiation, B-Lymphocyte
- CD8-Positive T-Lymphocytes
- Cancer Vaccines
- Female
- Histocompatibility Antigens Class II
- Immunization, Secondary
- Lymphocyte Depletion
- Melanoma, Experimental
- Mice
- Mice, Inbred C57BL
- Spleen
