High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens

After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10−5 of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10−4 to 3 × 10−3, which is 10–10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethé, V. Corbière, I. Théate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249–257)

A Phase II Study of Tg4010 (Mva-Muc1-Il2) in Association with Chemotherapy in Patients with Stage III/IV Non-small Cell Lung Cancer

BackgroundTG4010 is a recombinant viral vector expressing both the tumor-associated antigen MUC1 and Interleukine-2. This vector is based on the modified virus of Ankara, a significantly attenuated strain of vaccinia virus. TG4010 has been designed to induce or amplify a cellular immune response directed against tumor cells expressing MUC1.MethodsA multicenter, randomized phase II study has explored two schedules of the combination of TG4010 with first line chemotherapy in patients with stage IIIB/IV non-small cell lung cancer. In Arm 1, TG4010 was combined upfront with cisplatin (100 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and day 8). In Arm 2, patients were treated with TG4010 monotherapy until disease progression, followed by TG4010 plus the same chemotherapy as in Arm1. Response rate was evaluated according to RECIST. Median time to progression and median overall survival were calculated according to the Kaplan–Meier method.ResultsSixty-five patients were enrolled, 44 in Arm 1 and 21 in Arm 2, in accordance with the two stage Simon design of the statistical plan. In Arm 1, partial response was observed in 13 patients out of 37 evaluable patients (29.5% of the intent to treat population, 35.1% of the evaluable patients). In Arm 2, two patients experienced stable disease for more than 6 months with TG4010 alone (up to 211 days), in the subsequent combination with chemotherapy, one complete and one partial response were observed out of 14 evaluable patients. Arm 2 did not meet the criteria for moving forward to second stage. The median time to progression was 4.8 months for Arm 1. The median overall survival was 12.7 months for Arm 1 and 14.9 for Arm 2. One year survival rate was 53% for Arm 1 and 60% for Arm 2. TG4010 was well tolerated, mild to moderate injection site reactions, flu-like symptoms, and fatigue being the most frequent adverse reactions. A MUC1-specific cellular immune response was observed in lymphocyte samples from all responding patients evaluable for immunology.ConclusionsThe combination of TG4010 with standard chemotherapy in advanced non-small cell lung cancer is feasible and shows encouraging results. A randomized study evaluating the addition of TG4010 to first line chemotherapy in this population is in progress

Etude du rôle de retrovirus, d'oncogènes et de facteurs de croissance dans la transformation cellulaire maligne

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Etude du rôle de retrovirus, d'oncogènes et de facteurs de croissance dans la transformation cellulaire maligne

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Apport de la biologie moléculaire dans l'évaluation du pronostic du cancer de l'estomac.

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Involvement of the p53 tumor suppressor gene in Ph1-positive and Ph1-negative myeloid leukemia

SCOPUS: le.jinfo:eu-repo/semantics/publishe

LES ANDROGENES ONT-ILS UN ROLE THERAPEUTIQUE EN HEMATOLOGIE?

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Interleukin-10 and its implications for immunopathology.

Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

L'INTERLEUKINE 10, UNE NOUVELLE CYTOKINE IMMUNOSUPPRESSIVE ET ANTI-INFLAMMATOIRE

SCOPUS: sh.jinfo:eu-repo/semantics/publishe

TREATMENT OF ESSENTIAL THROMBOCYTHAEMIA BY ALPHA-INTERFERON

SCOPUS: le.jinfo:eu-repo/semantics/publishe