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Biomedical subjects

Marie-Christine Pandolfino

Publications and source records attributed to Marie-Christine Pandolfino.

7 recordsLinked to original sources
PubMed2006

Infusion of Melan-A/Mart-1 specific tumor-infiltrating lymphocytes enhanced relapse-free survival of melanoma patients.

Adoptive therapy of cancer has been mostly tested in advanced cancer patients using tumor-infiltrating lymphocytes (TIL). Following discouraging results likely due to poor tumor-specificity of TIL and/or high tumor burden, recent studies reiterate the enormous potential of this therapy, particularly in melanoma. We had performed a phase II/III randomised trial on 88 stage III melanoma patients, who received autologous TIL plus IL-2 or IL-2 alone, after complete tumour resection. We reported previously clinical and immunological results supporting the ability of tumor reactive TIL infusion to prevent further development of the melanoma disease and to increase overall survival of patients bearing only one tumor invaded lymph node. The absence of correlation between overall and disease-free survival and the amount of infused tumor-specific TIL suggested that therapeutic efficiency might depend on other parameters such as antigen specificity, function or persistence of TIL. Here we studied the recognition of a panel of 38 shared tumor-associated antigens (TAA) by TIL infused to the patients included in this assay, in order to determine if treatment outcome could correlate with particular antigen specificities of infused TIL. Results show that the infusion of Melan-A/MART-1 reactive TIL appears to be associated with a longer relapse-free survival for HLA-A2 patients. These results further support the relevance of Melan-A/MART-1 antigen as a prime target for immunotherapy protocols in melanoma.

Animals↗
PubMed2005

Adoptive transfer of tumor-reactive Melan-A-specific CTL clones in melanoma patients is followed by increased frequencies of additional Melan-A-specific T cells.

In this study, we report the adoptive transfer of highly tumor-reactive Melan-A-specific T cell clones to patients with metastatic melanoma, and the follow-up of these injected cells. These clones were generated from HLA-A*0201 patients by in vitro stimulations of total PBMC with the HLA-A*0201-binding Melan-A peptide analog ELAGIGILTV. Ten stage IV melanoma patients were treated by infusion of these CTL clones with IL-2 and IFN-alpha. The generated T cell clones, of effector/memory phenotype were selected on the basis of their ability to produce IL-2 in response to HLA-A*0201 Melan-A-positive melanoma lines. Infused clones were detected, by quantitative PCR, in the blood of three patients for periods ranging from 7 to 60 days. Six patients showed regression of individual metastases or disease stabilization, and one patient experienced a complete response, but no correlation was found between the detection of the infused clones in PBMC or tumor samples and clinical responses. Nonetheless, frequencies of Melan-A/A2-specific lymphocytes, measured by tetramer labeling, increased after treatment in most patients. In one of these patients, who showed a complete response, this increase corresponded to the expansion of new clonotypes of higher avidity than those detected before treatment. Together, our results suggest that infused CTL clones may have initiated an antitumor response that may have resulted in the expansion of a Melan-A-specific CTL repertoire.

Adoptive Transfer↗
PubMed2005

CD8(+) T lymphocytes reactive against Epstein-Barr virus antigens in skin lesions of a patient with Sézary syndrome.

Several studies have investigated the possible involvement of viral agents, and among them herpes viruses, in the development of cutaneous T-cell lymphoma. The aim of our study was to determine whether T cells specific to Epstein-Barr virus (EBV) antigens were detectable among tumor-infiltrating lymphocytes infiltrating cutaneous lesions of a patient with Sézary syndrome. To analyze responses to EBV, we used a transient SV-40 origin-defective transformed simian cells transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/viral protein combinations. This technique allowed the detection of EBV-specific T lymphocytes mainly directed against epitopes generated during the lytic cycle in the cutaneous lesions. This is, to our knowledge, the first description of the presence of EBV-specific T lymphocytes among tumor-infiltrating lymphocytes infiltrating the lesional skin of a patient with Sézary syndrome.

Antigens, Viral↗
PubMed2003

[Passive immunotherapy of melanoma].

The protocols of tumor immunotherapy have been largely developed in the past ten years due to the identification of many tumor antigens recognized specifically by CD8 and CD4 T lymphocytes. Among the various immunotherapies currently tested, passive immunotherapy (i.e injection of T lymphocytes generated and selected ex-vivo from blood or from the tumor), seems to be particularly promising. Indeed, three recent studies evidence the efficacy of such therapy in melanoma treatment. For the first time, a precise immunological follow-up was carried out, thus showing the correlation between the therapeutic benefit and the injection of tumor antigen specific T lymphocytes, and the survival and the preferential migration of these lymphocytes to the tumor sites. Although all the questions about optimal methods for this mode of therapy are not solved, these recent results constitute a major breakthrough in the field of the tumor immunotherapy.

CD4-Positive T-Lymphocytes↗
PubMed2002

Therapeutic efficacy of melanoma-reactive TIL injected in stage III melanoma patients.

Adoptive therapy for cancer using tumor-infiltrating lymphocytes (TIL) has mainly been investigated in cancer patients with advanced stage disease. The limited clinical success has not been encouraging, although this might be explained by poor TIL specificity and/or high tumor burden. To re-evaluate the effectiveness of adoptive therapy, we analyzed the capacity of tumor-reactive TIL injection in preventing the further development of disease in stage III melanoma patients after complete tumor resection. A phase II/III randomized trial was performed on 88 melanoma patients, who received autologous TIL plus interleukin-2 (IL-2) or IL-2 only. The duration of relapse-free survival was analyzed, taking into account the immunological specificity of injected TIL and the number of metastatic lymph nodes removed before treatment. Kaplan-Meyer analysis revealed that the injection of tumor-reactive TIL was statistically correlated with prolonged relapse-free survival in patients with only one metastatic lymph node. Therefore, improved clinical outcome could be obtained after adoptive therapy by selecting appropriate groups of patients and monitoring the specificity of the injected TIL populations.

Adjuvants, Immunologic↗
PubMed2002

Expression of CD94/NKG2-A on human T lymphocytes is induced by IL-12: implications for adoptive immunotherapy.

NK cell receptors (NKRs) are expressed on a subset of human T cells, predominantly CD8(+), within which they can modulate TCR-mediated functions. In an attempt to identify the mechanisms leading to NKR expression, we analyzed the capacity of IL-12 to modulate the expression by T cells of the components of the CD94/NKG2-A inhibitory receptor, a member of the C-type lectin-like family of NKR. We show that IL-12 induces the expression of NKG2-A and/or CD94 by CD8(+) T cells in culture, and that this induction was mediated neither by IFN-gamma nor by IL-15. We also show, using the redirected killing assay, that IL-12-induced expression of both CD94 and NKG2-A led to the acquisition by T cells of a functional inhibitory receptor. Expression of the CD94/NKG2-A inhibitory receptor was also induced by IL-12 during T cell Ag stimulation so that in the presence of this cytokine a high proportion of melanoma-reactive CTL induced from PBL by melanoma peptide stimulation expressed this receptor. This study emphasizes the implication of IL-12 in the modulation of immune responses through NKR induction.

Antigens, CD↗