Carbone DP et al. (2005) Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J Clin Oncol 23: 5099–5107
Immunologic targeting of cells using vaccines raised against the host's tumor offers the potential for specific, nontoxic cancer therapy. A recent trial has shown that custom-made peptide vaccination can induce or enhance cytotoxic lymphocyte (CTL) and interferon-γ (IFN-γ) response to p53 or K-ras in a range of cancers, without any toxicity.
Based on the presence of suitable mutations in p53 or K-ras, only 14% of patients screened for inclusion in the trial were eligible for specific immunization, emphasizing the difficulty of a broad clinical approach for custom-made peptide immunization. In all, 38 patients with mutations in p53 or K-ras underwent immunization with a cellular vaccine consisting of irradiated mutant peptide-pulsed peripheral-blood mononuclear cells. Of these, 10 patients had detectable CTL responses to the mutant protein after treatment, and 2 were positive at baseline. Positive IFN-γ responses were seen in 16 patients (42%) on treatment and 4 at baseline. Baseline immune response was enhanced after immunization. Of the 29 patients with evident disease, 5 went on to have a period of disease stability. Median survival times were 393 versus 98 days for a positive versus negative CTL response (P = 0.04) and 470 versus 88 days for a positive versus negative IFN-γ response (P = 0.02). Detectable CTL response and IFN-γ reaction were favorable prognostic markers.
CTL and IFN-γ response was associated with significantly prolonged survival, although the authors state that the degree to which this association was a direct consequence of the vaccination is unclear. Additional studies are currently underway.
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Lovegrove, C. Tumor-specific oncopeptide immunization associated with longer survival. Nat Rev Clin Oncol 2, 543 (2005). https://doi.org/10.1038/ncponc0304
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DOI: https://doi.org/10.1038/ncponc0304