Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma

Abstract

The cloning of the genes encoding cancer antigens has opened new possibilities for the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies.

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

“…Although different vaccination trials have reported a lack of a real advantage in the anti-tumor efficacy, 29 , 30 also in combination with the CTLA-4 blockade, 31 the gp100 209-217 (210M)-based vaccination, in combination with IL-2, showed clinical benefits in metastatic melanoma patients. 32 , 33 At TCR level, Schrama et al found the expansion of an oligoclonal gp100 210M-specific TCR repertoire from two patients receiving DTIC alone or in combination with low doses of IFN-α. 34 In agreement with these studies, in our study we observed that the 29 gp100 209-217 (210M)-specific clones sequenced from three patients were associated with a restricted TCR repertoire, irrespective of the treatment received (Figure 1░C).…”

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

“…Previous studies have demonstrated that activation of CD4 þ T cells is required for immunisation of CD8 þ T cells against cancer. For activation and maintenance of tumour-infiltrating CD8 þ T cells, CD4 þ T cells play an important role by secreting cytokines such as interleukin-2, which is required for CD8 þ T-cell growth and proliferation (Rosenberg et al, 1988(Rosenberg et al, , 1998Yoshino et al, 1992;Cheng et al, 1998;Wang and Rosenberg, 1999;Rosenberg, 2001;Wang, 2001;Zeng, 2001). Reduction of CD4 þ T lymphocytes by administration of anti-CD4 antibody allowed human lung cancer xenografts to form orthotopically in immuno-competent mice (Hunt et al, 2000).…”

Dendritic cells transduced with gp100 gene by RGD fiber-mutant adenovirus vectors are highly efficacious in generating anti-B16BL6 melanoma immunity in mice

“…Several human MHC class I-restricted peptides from gp100 have been identified, and vaccination strategies using synthetic gp100-derived peptides in conjunction with chemical adjuvant or autologous DCs have been evaluated in early phase I/II clinical trials. 24,25 The murine B16 melanoma model expresses most mouse homologs of these human MAAs, so it can be used to evaluate vaccine strategies in a preclinical setting. However, mice vaccinated with viral vectors encoding murine gp100 do not develop measurable murine gp100-specific immunity, and are apparently tolerant to murine gp100.…”