Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
The generation of CD4+ and CD8+ T cell responses from patients vaccinated with mutant Ras peptides corresponding to the patient's own Ras mutation (Meeting abstract).
Proc Annu Meet Am Soc Clin Oncol; 16:A1566 1997. Unique Identifier : AIDSLINE ICDB/98643566 Khleif SN; Abrams S; Allegra C; Bastian A; Bergmann E; Bernstein S; Chen A; Chung Y; Hamilton JM; Kohler DR; Morrison G; Schlom J; National Cancer Institute, Bethesda, MD
Abstract:
Cancers in humans are commonly associated with mutations in the Ras genes. These genes produce mutated proteins that are unique to cancer cells; codon 12 mutations form more than 90% of all ras mutations. To determine if peptides reflecting point mutations in Ras oncogenes are immunogenic in human, we conducted a phase I clinical trial at the NCI to study the feasibility of vaccinating patients (pts) with advanced cancers with specific codon 12 mutated ras peptides which correspond to the pt's tumor ras mutation (Gly to Val, Cys, or Asp). Twelve pts have been vaccinated subcutaneously with the corresponding peptide along with Detox as an adjuvant on four different peptides dose levels; (100, 500, 1000, and 1500 ug). Nine pts completed three planned vaccinations, two on level I, two on level II, three on level III, and one on level IV; three completed only one vaccination due to progressive disease. Immunological studies of the eight evaluable pts have been completed: we have found the generation of antigen-specific cellular immune responses resulting from the 3 vaccinations in 3 of 8 pts, demonstrated by the generation of MHC class II-restricted CD4+ response, and for the first time we demonstrated the generation of specific MHC class I (HLA-A2)-restricted CD8+ cytotoxic T cell (CTL) response, or the combination of both CD4+ and CD8+ response against the mutated but not the normal ras peptide. These responses were detected post but not prevaccination. In vitro stimulation with the immunizing peptide led to the generation of mutant specific CD4+ cell lines, while IVS with a 10 mer 'nested' peptide, which we identified for the first time as mutated ras CTL epitope, generated a mutant specific CD8+ CTL lines. To date, the treatment has been tolerated with no evidence of acute or delayed systemic side effects other than minor local reactions. So far no tumor responses have been seen. We are evaluating further stimulation of immune response with cytokines or the expansion of the specific cell lines for adoptive immune therapy.
Keywords: CD4-Positive T-Lymphocytes/*IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Cancer Vaccines/*ADMINISTRATION & DOSAGE Human *Point Mutation ras Proteins/*ADMINISTRATION & DOSAGE ABSTRACT 980228
M9820746
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Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
