Helper T-Cell Responses and Clinical Activity of a Melanoma Vaccine With Multiple Peptides From MAGE and Melanocytic Differentiation Antigens

Abstract

PurposeA phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins for these peptides include MAGE proteins, MART-1/MelanA, gp100, and tyrosinase.Patients and MethodsThirty-nine patients with stage IIIB to IV melanoma were vaccinated with this six-peptide mixture weekly at three dose levels, with a preceding phase I dose escalation and subsequent random assignment among the dose levels. Helper T-lymphocyte responses were assessed by in vitro proliferation assay and delayed-type hypersensitivity skin testing. Patients with measurable disease were evaluated for objective clinical response by Response Evaluation Criteria in Solid Tumors.ResultsVaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients. Among 17 patients with measurable disease, objective clinical responses were observed in two patients (12%), with response durations of 1 and 3.9+ years. Durable stable disease was observed in two additional patients for periods of 1.8 and 4.6+ years.ConclusionResults of this study support the safety and immunogenicity of a vaccine comprised of six melanoma helper peptides. There is also early evidence of clinical activity.

Characterization of the Class I-Restricted gp100 Melanoma Peptide-stimulated Primary Immune Response in Tumor-Free Vaccine-draining Lymph Nodes and Peripheral Blood

“…5A) further suggests this phenotype signature is not unique to naBve T cells. Moreover, between 1% and 10% of all peptide-specific 50 value for all patient lymph nodeT-cell responses was significantly higher than the mean log EC 50 value for PIVR Tcells (C).…”

“…Other vaccine strategies such as the incorportation of CD4 + helper T cell coactivation at priming will be required to induce long-term memory CD8 + T cells that are also functionally competent. Recent reports have identified potential class II-restricted peptides from melanocytic proteins such as tyrosinase, Melan-A/MART-1, and gp100, which bind to dominant HLA-DR haplotypes, and stimulate CD4 + T cell proliferation and delayed type hypersensitivity responses in immunized melanoma patients (50). The combination of such potential CD4 + helper T cell -specific antigens with class Irestricted melanoma peptides may result in clinically more effective melanoma vaccines.…”

A new era in anticancer peptide vaccines

“…38 A novel melanoma vaccine comprised of 6 melanoma-associated peptides as antigenic targets for melanoma-reactive T h cells was evaluated for safety and immunogenicity in a phase 1/2 trial. 40 Vaccination with the helper peptide vaccine was well tolerated. Proliferation assays revealed induction of T-cell responses to the melanoma helper peptides in 81% of patients.…”

Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine

“…þ lymphocyte activation and proliferation), 2,5,6 HLA class II-binding peptides (stimulating CD4 þ lymphocytes), 7,8 or a combination of both HLA class I and II-directed peptides. 9,10 Directly stimulating CD8 þ lymphocytes with HLA class I peptides makes intuitive sense, because class I molecules are present on most nonhematopoietic tumor cells, allowing CD8…”