A Quantitative Perspective on Surface Marker Selection for the Isolation of Functional Tumor Cells.

Much effort has gone into developing fluid biopsies of patient peripheral blood for the monitoring of metastatic cancers. One common approach is to isolate and analyze tumor cells in the peripheral blood. Widespread clinical implementation of this approach has been hindered by the current choice of targeting epithelial markers known to be highly variable in primary tumor sites.

Autoantibody profiling for lung cancer screening longitudinal retrospective analysis of CT screening cohorts.

Recommendations for lung cancer screening present a tangible opportunity to integrate predictive blood-based assays with radiographic imaging. This study compares performance of autoantibody markers from prior discovery in sample cohorts from two CT screening trials. One-hundred eighty non-cancer and 6 prevalence and 44 incidence cancer cases detected in the Mayo Lung Screening Trial were tested using a panel of six autoantibody markers to define a normal range and assign cutoff values for class prediction.

Pilot study of 1650-G: a simplified cellular vaccine for lung cancer.

Introduction: Cancer immunotherapy is a conceptually attractive since it is highly specific and can deal with disseminated disease with minimal impact on normal tissues. Early phase clinical trials have well established the ability of a variety of immunotherapeutic approaches to induce antigen specific immune responses in lung cancer patients. Although no immunotherapy is likely to be a panacea, recent data from randomized phase IIB studies offer promise of therapeutic activity in both early and late stage lung cancer.

Lung cancer-associated auto-antibodies measured using seven amino acid peptides in a diagnostic blood test for lung cancer.

Autoantibody profiling is a developing approach that incorporates immune recognition of myriad aberrant cancer proteins into a single diagnostic assay. We have previously described methodology to screen T7-phage NSCLC-cDNA libraries for phage-expressed proteins recognized by NSCLC-associated antibodies, and developed a multiplex assay that has excellent ability to discriminate NSCLC from control samples. This follow-up report describes the development and testing of a diagnostic autoantibody assay that uses seven amino-acid peptides as capture proteins.

Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non-small cell lung cancer.

The current study characterized peripheral blood mononuclear cells (PBMC) obtained from leukapheresis products of patients with non-small cell lung cancer (NSCLC) for cytokine release, the ability to incorporate tritiated thymidine following stimulation using PHA as well as the levels of both CD4 and CD8 regulatory T cells (Tregs) as defined by FoxP3 expression. Results were compared to normal donor PBMC obtained from buffy coat products. Heterogeneous levels of Th1 (gamma interferon and IL-2), Th2 (IL-10 and IL-13), pro-inflammatory (TNF-alpha and IL-6) and the hematopoietic inducing cytokine GMCSF were detected from both populations of PBMC as measured using ELISA.

Immunotherapy for lung cancer.

Immunotherapy is a conceptually attractive approach, because it is highly specific and can deal with disseminated disease with minimal impact on normal tissues. Ability to induce antigen-specific immune responses in patients with lung cancer is now well established in early-phase clinical trials using a variety of immunotherapeutic approaches. Although no immunotherapy is likely to be a panacea, randomized phase IIB studies offer promise of therapeutic activity in both early- and late-stage lung cancer.

Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells.

Only a handful of NSCLC patients have been included in dendritic cell (DC) vaccine clinical trials. We had previously reported a series of 16 individuals with stages IA-IIIB NSCLC who received autologous DC vaccines matured with dendritic cell/T cell-derived maturation factor (DCTCMF). Here we report the results of a continuation study with similar inclusion criteria, immunization protocol, and analysis, using an immature DC vaccine.

Profiling tumor-associated antibodies for early detection of non-small cell lung cancer.

Background: A blood test for non-small cell lung cancer (NSCLC) may be a valuable tool for use in a comprehensive lung cancer screening strategy. Here we report the potential of autoantibody profiling to detect early-stage and occult NSCLC.

Methods: T7-phage NSCLC cDNA libraries were screened with patient plasma to identify phage-expressed proteins recognized by tumor-associated antibodies.

Vaccines for lung cancer.

Immunotherapy is based on the knowledge that the immune system can distinguish cancerous cells from normal cells. Conceptually, this is an attractive adjuvant approach because it is highly specific and can deal with disseminated disease with minimal impact on normal tissues. In this review, we focus on strategies that use host immune machinery to generate anti-tumor effects, known as active immunotherapy.

Using protein microarray as a diagnostic assay for non-small cell lung cancer.

Rationale: Phenotypic and genotypic heterogeneity of lung cancer likely precludes the identification of a single predictive marker and suggests the importance of identifying and measuring multiple markers.

Objectives: We describe the use of a fluorescent protein microarray to identify and measure multiple non-small cell lung cancer-associated antibodies and show how simultaneous measurements can be combined into a single diagnostic assay.

Methods: T7 phage cDNA libraries of non-small cell lung cancer were first biopanned with plasma samples from normal subjects and patients with non-small cell lung cancer to enrich the component of tumor-associated proteins, and then applied to microarray slides.

Autologous dendritic cell vaccines for non-small-cell lung cancer.

Purpose: Therapeutic outcomes of definitively treated non-small-cell lung cancer (NSCLC) are unacceptably poor. A wealth of preclinical information, and a modest amount of clinical information indicate that dendritic cell (DC) vaccines have therapeutic potential. Only a handful of NSCLC patients have been included in DC clinical trials.

Identification of circulating antibodies to tumor-associated proteins for combined use as markers of non-small cell lung cancer.

Currently only a limited number of tumor markers for non-small cell lung cancer (NSCLC) are available. Antibodies to tumor-associated proteins may expand the number of available tumor markers for lung cancer and be used together in a serum profile to enhance sensitivity and specificity. In this study, we isolated 57 tumor-associated proteins from two NSCLC cDNA T7 phage libraries using biopan enrichment techniques with NSCLC patient and normal sera.

Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients.

Heat shock proteins (HSPs) are components of a physiologic stress response that are also over-expressed in various cancers including non-small cell lung cancer (NSCLC). During NSCLC serum-antibody screening of a NSCLC cDNA T7 phage library for immunogenic proteins we isolated HSP70 and HSP90 proteins. Isolation of these proteins suggested that corresponding antibodies could be elevated in NSCLC patient sera, a novel finding that could pilot their use as markers of NSCLC.

Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC).

Introduction: PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC) and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile.