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Biomedical subjects

Christophe L Nguyen

Publications and source records attributed to Christophe L Nguyen.

7 recordsLinked to original sources
PubMed2006

Radiofrequency ablation of lung malignancies.

Radiofrequency ablation is a new technology that has been used successfully to treat hepatic tumors. Recently, an increasing number of reports have described the use of radiofrequency ablation for primary and metastatic lung tumors. Although such early experience appears promising, many questions regarding patient selection, radiofrequency ablation technique, effectiveness of ablation on lung tumors, radiographic follow-up, and survival remain unanswered. This article addresses these issues and provides the thoracic surgeon with a current review of the application of radiofrequency ablation to lung tumors.

Animals↗
PubMed2005

Radiofrequency ablation of primary lung cancer: results from an ablate and resect pilot study.

STUDY OBJECTIVES: The role of radiofrequency ablation (RFA) for primary lung cancer remains poorly defined. The purpose of this "ablate and resect" pilot study was to evaluate the safety of performing RFA in patients with primary non-small cell lung cancer (NSCLC) and to characterize the histologic changes in tumor tissue following such ablation. DESIGN: This prospective study was undertaken at a single institution, and 10 patients were accrued from June 2002 to June 2003. Eligible patients included those with clinical stage I or II disease. RFA of the tumor was performed through a standard thoracotomy followed by conventional lobectomy and lymph node dissection. Extent of cell death was determined histologically. MEASUREMENTS AND RESULTS: Following the exclusion of two patients, the treated portions of eight tumors were examined for tumor cell viability. Gross inspection and routine histologic staining could not reliably identify the "immediately ablated" tissue. However, using a supravital staining technique, the treated areas from seven of the eight tumors (87.5%) demonstrated > 80% nonviability (100% nonviability was noted in the treated areas from three of the eight tumors). No bleeding or thermal complications were noted at the time of RFA, and none of the patients had skin burns at the electrode dispersive pad sites. CONCLUSIONS: RFA of primary NSCLC is feasible and can be performed safely in the setting of an open thoracotomy. Complete tumor cell necrosis, as determined by supravital staining, was noted in the treated areas from three of eight tumors (37.5%). Such complete ablation was observed in the treated areas from smaller tumors (< 2 cm), whereas the treated areas from larger tumors demonstrated incomplete ablation. Additional investigation with histopathologic correlation is needed to fully assess the long-term efficacy of RFA for NSCLC.

Aged↗
PubMed2004

Paracrine release of IL-12 stimulates IFN-gamma production and dramatically enhances the antigen-specific T cell response after vaccination with a novel peptide-based cancer vaccine.

Interleukin-12 can act as a potent adjuvant for T cell vaccines, but its clinical use is limited by toxicity. Paracrine administration of IL-12 could significantly enhance the response to such vaccines without the toxicity associated with systemic administration. We have developed a novel vaccine delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of a sustained-release delivery system and a potent adjuvant. To test the efficacy of paracrine IL-12, we incorporated this cytokine into F2 gel matrix and monitored the response of OT-1 T cells in an adoptive transfer model. Recipient mice were vaccinated with F2 gel/SIINFEKL, F2 gel/SIINFEKL/IL-12 (paracrine IL-12), or F2 gel/SIINFEKL plus systemic IL-12 (systemic IL-12). Systemic levels of IL-12 were lower in paracrine IL-12-treated mice, suggesting that paracrine administration of IL-12 may be associated with less toxicity. However, paracrine administration of IL-12 was associated with an enhanced Ag-specific T cell proliferative and functional response. Furthermore, paracrine IL-12 promoted the generation of a stable, functional memory T cell population and was associated with protection from tumor challenge. To study the mechanisms underlying this enhanced response, wild-type and gene-deficient mice were used. The enhanced immune response was significantly reduced in IFN-gamma(-/-) and IL-12R beta 2(-/-) recipient mice suggesting that the role of IL-12 is mediated, at least in part, by host cells. Collectively, the results support the potential of F2 gel matrix as a vaccine delivery system and suggest that sustained paracrine release of IL-12 has potential clinical application.

Adjuvants, Immunologic↗
PubMed2003

Mechanisms of enhanced antigen-specific T cell response following vaccination with a novel peptide-based cancer vaccine and systemic interleukin-2 (IL-2).

Systemic interleukin-2 (IL-2) therapy has been shown to enhance the clinical efficacy of peptide-based cancer vaccines. However, the mechanisms involved in this complex response remain poorly defined. IL-2 is known to be a potent T cell growth factor, but recent studies suggest that IL-2 is also involved in the regulation of T cell immune responses by increasing the susceptibility of proliferating T cells to apoptosis. Using an adoptive transfer model, we demonstrate that the administration of systemic IL-2 significantly enhances the primary and memory immune responses following peptide-based vaccination. In order to define the mechanisms of IL-2 therapy on the antigen-specific T cell response, the kinetics of T cell proliferation, apoptosis, and trafficking were explored. Systemic IL-2 therapy did not appear to alter the kinetics of T cell proliferation immediately following vaccination, but did prolong the proliferative response. Furthermore, IL-2 therapy did not significantly influence apoptosis of proliferating T cells. Such therapy did, however, potentiate L-selectin (CD62L) downregulation on activated antigen-specific T cells, and altered their trafficking confirming their potential therapeutic value. Our findings support the use of systemic IL-2 following peptide-based vaccination, and suggest that IL-2 therapy enhances the primary and memory immune responses by prolonging the proliferative response and altering the trafficking of antigen-specific T cells.

Animals↗
PubMed2003

Transfer of TCR genes into mature T cells is accompanied by the maintenance of parental T cell avidity.

The adoptive transfer of tumor-specific T cells expanded in vitro can be of significant therapeutic value in select cancer patients. This strategy is limited though, as it is often difficult, if not impossible, to obtain T cells of clinical value. The transfer of TCR genes to mature T cells to generate tumor-reactive T cells provides a potential mechanism to overcome these limitations. To evaluate the feasibility of such an approach and the quality of the resulting T cells, we generated replication-deficient retroviral vectors using the well-characterized OT-1 TCR genes. After transducing murine T cells, we were able to expand large numbers of Ag-specific T cells that were functionally active against tumor cells expressing the relevant Ag. Furthermore, we found that T cells expressing retrovirally encoded TCR had avidity that was similar to that of the parental clone. This maintenance of avidity was despite variable expression of the retrovirally encoded TCR and the presence of potentially competing endogenous TCRs. These results suggest that the inherent qualities of the TCR, as dictated by the coding sequence, are the most critical parameters in the generation of high-avidity T cells.

Animals↗
PubMed2002

Systemic administration of IL-15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells.

The systemic administration of IL-2 can act as a potent adjuvant for T cell-directed vaccine strategies. However, not only is the administration of IL-2 potentially toxic, but recent evidence suggests that it may also paradoxically limit the duration and magnitude of the cytotoxic T cell response. A recently identified cytokine, IL-15, shares many properties with IL-2 and may provide a preferential means of augmenting T cell-directed vaccine responses. Although well characterized in vitro, there are few data on the ability of IL-15 to augment T cell-mediated responses in vivo. We therefore evaluated the ability of systemic IL-15 to function as a T cell adjuvant in a murine vaccine model. To establish a population of easily identifiable Ag-responsive T cells, naive CD8(+) (OT-1) T cells were first adoptively transferred into mice. Vaccination with peptide-pulsed dendritic cells induced a modest expansion of OT-1 T cells. The addition of systemic IL-15 for 7 days following vaccination resulted in a significant increase in the expansion of responding T cells in the PBL, spleen, and lymph nodes. Importantly, the responding T cells were cytotoxic and maintained a Tc1-biased phenotype. We did not observe either enhanced resistance to activation-induced cell death or preferential generation of memory T cells as a result of treatment with IL-15 compared with IL-2. These studies show for the first time that IL-15 is capable of augmenting the primary CD8(+) T cell response to vaccination and contribute to the basis for future experiments exploring the clinical role of IL-15.

Adjuvants, Immunologic↗