Regression of Extensive Pulmonary Metastases in Mice by Adoptive Transfer of Antigen-Specific CD8+ CTL Reactive Against Tumor Cells Expressing a Naturally Occurring Rejection Epitope
| Autor: | J. Andrew Bristol, Scott I. Abrams, Elwood McDuffie, Mary Hilburger Ryan |
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| Rok vydání: | 2001 |
| Předmět: |
Adoptive cell transfer
Immunoconjugates Lung Neoplasms medicine.drug_class T cell Immunology chemical and pharmacologic phenomena Biology Monoclonal antibody Immunotherapy Adoptive Epitope Cell Line Abatacept Mice Antigens CD In vivo medicine Animals Immunology and Allergy CTLA-4 Antigen Mice Inbred BALB C Carcinoma Provirus Antigens Differentiation CTL medicine.anatomical_structure Cytokines Female Sarcoma Experimental CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 167:4286-4292 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.167.8.4286 |
| Popis: | In this study, we developed a mouse model of adoptive immunotherapy reflecting immune recognition of syngeneic tumor cells naturally expressing an endogenous rejection Ag. Specifically, in a pulmonary metastases model, we examined the potency and maintenance of an antitumor CD8+ CTL response in vivo, as well as its effectiveness against an “extensive” tumor burden. The approach taken was to first generate tumor-specific CTL from mice challenged with the CMS4 sarcoma coadministered with anti-CTLA4 mAb, which has been shown to facilitate the induction of Ag-specific T cell responses in vivo. An H-2Ld-restricted nonamer peptide, derived from an endogenous murine leukemia provirus was identified as a CMS4-reactive CTL epitope based upon the following: CTL cross-recognition of another syngeneic tumor cell line (CT26 colon carcinoma) previously characterized to express that gene product; sensitization of Ag-negative lymphoblasts or P815 targets with the peptide; and by cold target inhibition assays. In vivo, the adoptive transfer of CMS4-reactive CTL (≥1 × 106) resulted in nearly the complete regression of 3-day established lung metastases. Furthermore, mice that rejected CMS4 following a single adoptive transfer of CTL displayed antitumor activity to a rechallenge 45 days later, not only in the lung, but also at a s.c. distal site. Lastly, the adoptive transfer of CTL to mice harboring extensive pulmonary metastases (>150 nodules) led to a substantial reduction in tumor burden. Overall, these data suggest that the adoptive transfer of tumor-specific CTL may have therapeutic potential for malignancies that proliferate in or metastasize to the lung. |
| Databáze: | OpenAIRE |
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