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Active specific immunotherapy against occult brain metastasis
Weixin Lu1, Jindong Su, Lee Su Kim
1Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
We determined whether lyophilized High Five (H5) insect cells engineered to produce IFN-beta (H5BVIFN-beta) could induce systemic immunity against occult brain metastases. C3H/HeN mice were injected s.c. with syngeneic UV-2237M fibrosarcoma or K-1735M2 melanoma cells. Intralesional injection of 2 x 10(6) lyophilized H5BVIFN-beta cells produced complete regression of the s.c. tumors. Six weeks later, UV-2237M fibrosarcoma cells or K-1735M2 melanoma cells were injected into the internal carotid artery of naive or treated mice. UV-2237M brain metastases developed in naive mice or mice cured of K-1735M2 tumors but not in mice cured of UV-2237M tumors. Similarly, K-1735M2 brain metastases developed in naive mice or mice cured of UV-2237M fibrosarcomas but not in mice cured of K-1735M2 melanoma. In the next set of studies, mice were injected s.c. with UV-2237M fibrosarcoma cells. On day 7, UV-2237M fibrosarcoma cells or K-1735M2 cells were implanted into the internal carotid artery, and on day 10, the s.c. tumors were injected with lyophilized H5BVIFN-beta. Both the s.c. tumors and the occult brain metastases produced from carotid injections were eradicated in a tumor-specific manner. The regression of the brain metastases was abrogated by depletion of CD4(+) or CD8(+) cells from immunized mice. These results demonstrate that specific systemic immunity can be induced by lyophilized H5BVIFN-beta and that the resultant immune response can eliminate established brain metastasis.
Insights
Lyophilized insect cells producing interferon-beta (IFN-beta) can induce systemic immunity to eliminate brain metastases. This approach eradicates established tumors and prevents metastasis recurrence in mice.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Occult brain metastases pose a significant challenge in cancer treatment.
- Developing strategies to induce systemic immunity against brain tumors is crucial.
- Insect cell-based therapies offer a novel approach for cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of lyophilized High Five (H5) insect cells engineered to produce interferon-beta (H5BVIFN-beta) in inducing systemic immunity against occult brain metastases.
- To determine if this induced immunity can eradicate established brain metastases in a tumor-specific manner.
Main Methods:
- C3H/HeN mice bearing fibrosarcoma or melanoma tumors were treated with intralesional injections of lyophilized H5BVIFN-beta cells.
- Brain metastases were established by intra-arterial injection of tumor cells.
- The ability of the induced systemic immunity to eradicate established brain metastases was assessed.
- The role of CD4(+) and CD8(+) cells in the immune response was investigated through cell depletion studies.
Main Results:
- Intralesional injection of lyophilized H5BVIFN-beta cells led to complete regression of primary tumors.
- Mice cured of primary tumors exhibited specific immunity, preventing the development of subsequent brain metastases.
- Treatment eradicated both primary tumors and established brain metastases in a tumor-specific manner.
- The regression of brain metastases was dependent on CD4(+) and CD8(+) T cells.
Conclusions:
- Lyophilized H5BVIFN-beta cells can induce potent and specific systemic anti-tumor immunity.
- This approach is effective in eradicating established brain metastases.
- The findings highlight the potential of insect cell-based immunotherapy for treating metastatic brain cancer.
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