Long-term survival and complete cures of B16 melanoma-carrying animals after therapy with tumor-targeted IL-2 and sea
Rosendahl, Alexander ; Kristensson, Karin ; Carlsson, Mats ; Skartved, Niels Jørgen ; Riesbeck, Kristian LU
; Søgaard, Morten
and Dohlsten, Mikael
(1999)
In International Journal of Cancer
81(1).
p.156-163
- Abstract
The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. To engineer SAg for cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215 tumor-reactive antibody. Strong reduction of lung metastasis was seen in mice carrying established lung metastases of the poorly immunogenic B16-C215 melanoma after Fab-SEA therapy. However, important anti-tumor effector functions, such as IFN-γ secretion and CTL activity, gradually declined during therapy. In this study, we show that Fab-SEA immunotherapy is strongly potentiated by Fab-IL-2 coadministration. Combined Fab-IL-2 and Fab- SEA therapy prolongs the immune response in vivo, limits the development... (More)
The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. To engineer SAg for cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215 tumor-reactive antibody. Strong reduction of lung metastasis was seen in mice carrying established lung metastases of the poorly immunogenic B16-C215 melanoma after Fab-SEA therapy. However, important anti-tumor effector functions, such as IFN-γ secretion and CTL activity, gradually declined during therapy. In this study, we show that Fab-SEA immunotherapy is strongly potentiated by Fab-IL-2 coadministration. Combined Fab-IL-2 and Fab- SEA therapy prolongs the immune response in vivo, limits the development of immunological unresponsiveness and promotes maximal anti-tumor effects. Significantly prolonged survival was noted in tumor-carrying animals treated with Fab-SEA/Fab-IL-2 as compared with Fab-SEA or Fab-IL-2 alone. Combination therapy resulted in complete cure in 90% of tumor-bearing animals, whereas only 10% long-term survival was seen in Fab-SEA or Fab-IL-2-treated animals. Single Fab-SEA therapy induced a hyporesponsive state after 2 cycles of treatment. In contrast, the immune response after combination therapy was characterized by substantially augmented IFN-γ and TNF-α production and strong CTL activity. Our data demonstrate that combined Fab-SEA and Fab-IL-2 therapy prolongs the immune response in vivo and induced long-term survival of more than 90% of the animals carrying the highly aggressive B16 melanoma.
(Less)
- author
- Rosendahl, Alexander
; Kristensson, Karin
; Carlsson, Mats
; Skartved, Niels Jørgen
; Riesbeck, Kristian
LU
; Søgaard, Morten
and Dohlsten, Mikael
- publishing date
- 1999-03-22
- type
- Contribution to journal
- publication status
- published
- subject
- in
- International Journal of Cancer
- volume
- 81
- issue
- 1
- pages
- 156 - 163
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:10077167
- scopus:0033044226
- ISSN
- 0020-7136
- DOI
- 10.1002/(SICI)1097-0215(19990331)81:1<156::AID-IJC25>3.0.CO;2-H
- language
- English
- LU publication?
- no
- id
- c30113ac-2cb1-4f69-be8e-5907f32541c1
- date added to LUP
- 2019-06-07 15:19:04
- date last changed
- 2025-06-12 01:34:53
@article{c30113ac-2cb1-4f69-be8e-5907f32541c1,
abstract = {{<p>The bacterial superantigen (SAg) staphylococcal enterotoxin A (SEA) is a potent inducer of CTL activity and cytokine production in vivo. To engineer SAg for cancer immunotherapy, we genetically fused SEA to a Fab fragment of the C215 tumor-reactive antibody. Strong reduction of lung metastasis was seen in mice carrying established lung metastases of the poorly immunogenic B16-C215 melanoma after Fab-SEA therapy. However, important anti-tumor effector functions, such as IFN-γ secretion and CTL activity, gradually declined during therapy. In this study, we show that Fab-SEA immunotherapy is strongly potentiated by Fab-IL-2 coadministration. Combined Fab-IL-2 and Fab- SEA therapy prolongs the immune response in vivo, limits the development of immunological unresponsiveness and promotes maximal anti-tumor effects. Significantly prolonged survival was noted in tumor-carrying animals treated with Fab-SEA/Fab-IL-2 as compared with Fab-SEA or Fab-IL-2 alone. Combination therapy resulted in complete cure in 90% of tumor-bearing animals, whereas only 10% long-term survival was seen in Fab-SEA or Fab-IL-2-treated animals. Single Fab-SEA therapy induced a hyporesponsive state after 2 cycles of treatment. In contrast, the immune response after combination therapy was characterized by substantially augmented IFN-γ and TNF-α production and strong CTL activity. Our data demonstrate that combined Fab-SEA and Fab-IL-2 therapy prolongs the immune response in vivo and induced long-term survival of more than 90% of the animals carrying the highly aggressive B16 melanoma.</p>}},
author = {{Rosendahl, Alexander and Kristensson, Karin and Carlsson, Mats and Skartved, Niels Jørgen and Riesbeck, Kristian and Søgaard, Morten and Dohlsten, Mikael}},
issn = {{0020-7136}},
language = {{eng}},
month = {{03}},
number = {{1}},
pages = {{156--163}},
publisher = {{John Wiley & Sons Inc.}},
series = {{International Journal of Cancer}},
title = {{Long-term survival and complete cures of B16 melanoma-carrying animals after therapy with tumor-targeted IL-2 and sea}},
url = {{http://dx.doi.org/10.1002/(SICI)1097-0215(19990331)81:1<156::AID-IJC25>3.0.CO;2-H}},
doi = {{10.1002/(SICI)1097-0215(19990331)81:1<156::AID-IJC25>3.0.CO;2-H}},
volume = {{81}},
year = {{1999}},
}