Induction of antitumor immunity after cure of pulmonary metastases, using staphylococcal enterotoxin B and bispecific antibody
Autor: | David C. Rice, Andrei I. Chapoval, Louis Porter, Heidi Nelson |
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Rok vydání: | 1999 |
Předmět: |
Cancer Research
Cellular immunity Lung Neoplasms Antibodies Neoplasm CD8 Antigens medicine.medical_treatment Immunology chemical and pharmacologic phenomena Lymphocyte Activation Enterotoxins Mice Immune system Antigen Antibodies Bispecific Tumor Cells Cultured medicine Superantigen Animals Immunology and Allergy Cytotoxic T cell Hypersensitivity Delayed Melanoma Mice Inbred C3H business.industry Immunization Passive Immunotherapy Acquired immune system Oncology CD4 Antigens Female Immunization business Immunologic Memory Neoplasm Transplantation CD8 T-Lymphocytes Cytotoxic |
Zdroj: | Cancer Immunology, Immunotherapy. 48:230-238 |
ISSN: | 1432-0851 0340-7004 |
Popis: | The combination of staphylococcal enterotoxin B (SEB) and anti-p97 x anti-CD3 bispecific antibody (bsAb) cures 60%-80% of mice with established pulmonary metastases of the syngeneic p97+ murine melanoma, CL62. We investigated the ability of cured mice to generate protective antitumor immunity. In tumor rechallenge experiments, CL62-cured mice developed protective immunity against rechallenge with CL62. The majority of mice also rejected the p97-negative parental cell line, K1735, indicating an immune response to tumor antigens common to both cell lines that were not bsAb-targeted. A significant humoral response developed against p97 antigen, but not against other antigens common to both CL62 and K1735. That the majority of cured mice nevertheless rejected K1735 suggests that tumor immunity is not antibody-dependent. Evidence of cellular immunity was obtained from the results of delayed-type hypersensitivity, proliferation and cytotoxicity assays, which revealed the presence of tumor-specific memory in bsAb-treated, CL62-cured mice. CD8+ T cells from cured, but not control mice were able to lyse tumor; however, memory CD4 cells had no cytolytic function. In vivo, however, both CD4 and CD8 T cells were required for effective protective immunity. These studies demonstrate that treatment with SEB and bsAb not only confers passive immune effects of tumor eradication, but also actively promotes the generation of a host antitumor immune response. |
Databáze: | OpenAIRE |
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