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Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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 x 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.
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K. Liu, S. A. Caldwell, K. M. Greeneltch, D. Yang, and S. I. Abrams CTL Adoptive Immunotherapy Concurrently Mediates Tumor Regression and Tumor Escape J. Immunol., March 15, 2006; 176(6): 3374 - 3382. [Abstract] [Full Text] [PDF]
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K. Liu, S. A. Caldwell, and S. I. Abrams Immune Selection and Emergence of Aggressive Tumor Variants as Negative Consequences of Fas-Mediated Cytotoxicity and Altered IFN-{gamma}-Regulated Gene Expression Cancer Res., May 15, 2005; 65(10): 4376 - 4388. [Abstract] [Full Text] [PDF]
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K. Liu, S. A. Caldwell, and S. I. Abrams Cooperative Disengagement of Fas and Intercellular Adhesion Molecule-1 Function in Neoplastic Cells Confers Enhanced Colonization Efficiency Cancer Res., February 1, 2005; 65(3): 1045 - 1054. [Abstract] [Full Text] [PDF]
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M. Chakraborty, S. I. Abrams, C. N. Coleman, K. Camphausen, J. Schlom, and J. W. Hodge External Beam Radiation of Tumors Alters Phenotype of Tumor Cells to Render Them Susceptible to Vaccine-Mediated T-Cell Killing Cancer Res., June 15, 2004; 64(12): 4328 - 4337. [Abstract] [Full Text] [PDF]
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S. A. Caldwell, M. H. Ryan, E. McDuffie, and S. I. Abrams The Fas/Fas Ligand Pathway Is Important for Optimal Tumor Regression in a Mouse Model of CTL Adoptive Immunotherapy of Experimental CMS4 Lung Metastases J. Immunol., September 1, 2003; 171(5): 2402 - 2412. [Abstract] [Full Text] [PDF]
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K. Liu and S. I. Abrams Alterations in Fas Expression Are Characteristic of, But Not Solely Responsible for, Enhanced Metastatic Competence J. Immunol., June 15, 2003; 170(12): 5973 - 5980. [Abstract] [Full Text] [PDF]
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A. Rosato, S. D. Santa, A. Zoso, S. Giacomelli, G. Milan, B. Macino, V. Tosello, P. Dellabona, P.-L. Lollini, C. De Giovanni, et al. The Cytotoxic T-Lymphocyte Response against a Poorly Immunogenic Mammary Adenocarcinoma Is Focused on a Single Immunodominant Class I Epitope Derived from the gp70 Env Product of an Endogenous Retrovirus Cancer Res., May 1, 2003; 63(9): 2158 - 2163. [Abstract] [Full Text] [PDF]
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N. Meidenbauer, J. Marienhagen, M. Laumer, S. Vogl, J. Heymann, R. Andreesen, and A. Mackensen Survival and Tumor Localization of Adoptively Transferred Melan-A-Specific T Cells in Melanoma Patients J. Immunol., February 15, 2003; 170(4): 2161 - 2169. [Abstract] [Full Text] [PDF]
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