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1.
J Clin Oncol ; 23(22): 5099-107, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-15983396

ABSTRACT

PURPOSE: To determine the ability to induce tumor-specific immunity with individual mutant K-ras-or p53-derived peptides and to monitor clinical outcome. PATIENTS AND METHODS: Patients in varying stages of disease underwent genetic analysis for mutations in K-ras and p53. Thirty-nine patients were enrolled. Seventeen-mer peptides were custom synthesized to the corresponding mutation. Baseline immunity was assessed for cytotoxic T-lymphocyte (CTL) response and interferon gamma (IFN-gamma) release from mutant peptide-primed lymphocytes. Patients' peripheral-blood mononuclear cells were pulsed with the corresponding peptide, irradiated, and applied intravenously. Patients were observed for CTL, IFN-gamma, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony-stimulating factor responses, for treatment-related toxicity, and for tumor response. RESULTS: No toxicity was observed. Ten (26%) of 38 patients had detectable CTL against mutant p53 or K-ras, and two patients were positive for CTL at baseline. Positive IFN-gamma responses occurred in 16 patients (42%) after vaccination, whereas four patients had positive IFN-gamma reaction before vaccination. Of 29 patients with evident disease, five experienced a period of stable disease. Favorable prognostic markers were detectable CTL activity and a positive IFN-gamma reaction but not IL-5 release. Median survival times of 393 v 98 days for a positive versus negative CTL response (P = .04), respectively, and of 470 v 88 days for a positive versus negative IFN-gamma response (P = .02), respectively, were detected. CONCLUSION: Custom-made peptide vaccination is feasible without any toxicity. CTL and cytokine responses specific to a given mutation can be induced or enhanced with peptide vaccines. Cellular immunity to mutant p53 and K-ras oncopeptides is associated with longer survival.


Subject(s)
Cancer Vaccines , Genes, p53 , Genes, ras , Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Adult , Aged , Cytokines/biosynthesis , Cytokines/immunology , Female , Humans , Interferon-gamma/metabolism , Male , Middle Aged , Neoplasms/immunology , Prognosis , Survival Analysis , Treatment Outcome , Tumor Suppressor Protein p53
2.
Blood ; 86(11): 4063-75, Dec.1 1995.
Article in English | MedCarib | ID: med-1757

ABSTRACT

Adult T-cell leukemia (ATL) is a malignancy of mature lumphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months: no chemotherapy regimen appears successful inducing long-term disease-free survival. The scientific basis of the present study is the ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this differnce, we administered anti-Tac armed with Yttrium-90 (Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5-to 15-mCi doses used, 9 of 16 evaluable patients responded to Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.(AU)


Subject(s)
Adult , Middle Aged , Aged , Female , Humans , Male , Human T-lymphotropic virus 1/radiation effects , Receptors, Interleukin-2/therapeutic use , Radioimmunotherapy , Yttrium Radioisotopes/therapeutic use , Antibodies, Monoclonal/therapeutic use , United States , Jamaica , Trinidad and Tobago , Guyana , Japan , Haiti , Grenada , Saint Vincent and the Grenadines , Cross-Sectional Studies
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