Cytolytic T‐cell responses of cancer patients vaccinated with a MAGE antigen

Abstract

'Cancer-germline' genes such as the MAGE gene family are expressed in many tumors and in male germline cells but not in normal tissues. They encode shared tumor-specific antigens, which have been used in therapeutic vaccination trials of metastatic melanoma patients. To establish whether there is a correlation between tumoral regressions and T-cell responses against the vaccine antigen, we evaluated the responses of patients vaccinated with a MAGE-3 antigenic peptide or a recombinant virus coding for the peptide. Blood lymphocytes were stimulated with antigenic peptide followed by detection with tetramer, T-cell cloning, and TCR analysis. In 4/9 regressor patients and in 1/14 progressors we found a low level, usually monoclonal cytolytic T lymphocyte response against the MAGE-3 peptide.

Two new tumor‐specific antigenic peptides encoded by gene MAGE‐C2 and presented to cytolytic T lymphocytes by HLA‐A2

“…14 The clinical evolution was characterized by complete and durable regression of all cutaneous metastases, which was associated with a monoclonal CTL response to one of the vaccine antigens, the MAGE-A3 peptide. An autologous melanoma cell line was established from an invaded lymph node that had been resected, and was used in vitro to stimulate autologous CD8 ϩ blood lymphocytes collected from the patient after the immunization.…”

“…Melanoma patient EB81 showed complete regression of cutaneous metastatic lesions after repetitive vaccination with a recombinant canarypox virus of the ALVAC type encoding 2 HLA-A1-restricted peptides derived from MAGE-A1 and MAGE-A3. 14,15 This regression has been durable and was associated with a monoclonal CTL response to one of the vaccine antigens, the MAGE-A3 peptide. We established a tumor cell line from an invaded lymph node that had been resected from this patient, and we used it to stimulate autologous blood lymphocytes collected at the time of tumor regression.…”

Immune Responses to a Class II Helper Peptide Epitope in Patients with Stage III/IV Resected Melanoma

“…ϩ CTLs against MHC class I-restricted epitopes derived from these antigens have been demonstrated in a number of clinical trials in which patients were vaccinated with peptides in aqueous solution or with various adjuvants (7)(8)(9)(10)(11). In contrast, induction of cognate CD4 ϩ helper T lymphocytes by vaccination has not been pursued as extensively, and in the few clinical trials in which CD4…”

Biomarkers for the Development of Cancer Vaccines

“…It is well established that tumors from a variety of sources share multiple antigens. Examples include the melanoma antigen gene (MAGE), New York esophageal squamous cell carcinoma 1 (NY-ESO1) and mucin 1 (MUC1) [26,27]. Given that the proposed mechanism of action requires that the vaccine will be broken down into its constituent peptides, it follows that the HLA type of the vaccine is of secondary importance, since antigen processing will occur regardless of the patient's tissue-type.…”