A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by geneMAGE-3

Abstract

Vaccination of melanoma patients with tumor-specific antigens recognized by cytolytic T lymphocytes (CTL) produces significant tumor regressions in a minority of patients. These regressions appear to occur in the absence of massive CTL responses. To detect low-level responses, we resorted to antigenic stimulation of blood lymphocyte cultures in limiting dilution conditions, followed by tetramer analysis, cloning of the tetramer-positive cells, and T-cell receptor (TCR) sequence analysis of the CTL clones that showed strict specificity for the tumor antigen. A monoclonal CTL response against a MAGE-3 antigen was observed in a melanoma patient, who showed partial rejection of a large metastasis after treatment with a vaccine containing only the tumor-specific antigenic peptide. Tetramer analysis after in vitro restimulation indicated that about 1͞40,000 postimmunization CD8 ؉ blood lymphocytes were directed against the antigen. The same TCR was present in all of the positive microcultures. TCR evaluation carried out directly on blood lymphocytes by PCR amplification led to a similar frequency estimate after immunization, whereas the TCR was not found among 2.5 ؋ 10 6 CD8 ؉ lymphocytes collected before immunization. Our results prove unambiguously that vaccines containing only a tumor-specific antigenic peptide can elicit a CTL response. Even though they provide no information about the effector mechanisms responsible for the observed reduction in tumor mass in this patient, they would suggest that low-level CTL responses can initiate tumor rejection.

Targeting dendritic cells with antigen via dendritic cell-associated promoters

“…However, the detection of specific cellular responses is not always detected concomitantly with tumor regression. 37 The limited capacity of the DC-specific promoters used in this study to induce immunity may be related to the relatively low expression levels they induce in DC. Increasing their strength by adding enhancer-type elements like those recognized by CIITA (class II, major histocompatibility complex, transactivator) might be important to improve their activity.…”

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

“…Clinical trials with MAGE peptides are currently carried out, mainly for melanoma (Parmiani et al, 2002). Melanoma regression following vaccination with MAGE-3 peptide was demonstrated, with low-frequency CTL response (Coulie et al, 2001). Another study (Nishiyama et al, 2001) describes the use of autologous DC pulsed with an HLA-A24-restricted MAGE-A3-encoded peptide.…”

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

“…After washing, the cells were cultured in RPMI medium supplemented with 10% human AB serum, 10 ng/mL IL-7 (CellGenix), 10 ng/mL IL-4 and 30 IU/mL IL-2 (Chiron, Ratingen, Germany) at a density of 2 3 10 5 cells per well in 96-well round-bottom plates. 23 Positive control wells were stimulated with MART-1 peptide (ELAGI-GILTV). Negative control wells were stimulated with an HCVderived peptide (KLVALGINAV).…”