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Biomedical subjects

Michael L Salgaller

Publications and source records attributed to Michael L Salgaller.

6 recordsLinked to original sources
PubMed2003

Dendritic cells efficiently acquire and present antigen derived from lung cancer cells and induce antigen-specific T-cell responses.

Active immunotherapy of cancer requires the availability of a source of tumor antigens. To date, no such antigen associated with lung cancer has been identified. We have therefore investigated the ability of dendritic cells (DC) to capture whole irradiated human lung tumor cells and to present a defined surrogate antigen derived from the ingested tumor cells. We also describe an in vitro system using a modified human adenocarcinoma cell line (A549-M1) that expresses the well-characterized, immunogenic influenza M1 matrix protein as a surrogate tumor antigen. Peripheral blood monocyte-derived DC, when co-cultured with sub-lethally irradiated A549 cells or primary lung tumor cells derived from surgical resection of non-small cell carcinoma (NSCLC), efficiently ingested the tumor cells as determined by flow cytometry analysis and confocal microscopic examination. More importantly, DC loaded with irradiated A549-M1 cells efficiently processed and presented tumor cell-derived M1 antigen to T cells and elicited antigen-specific immune responses that included IFNgamma release from an M1-specific T-cell line, expansion of M1 peptide-specific Vbeta17+ and CD8+ peripheral T cells and generation of M1-specific cytotoxic T lymphocytes (CTL). We also compared DC loaded with irradiated tumor cells to those loaded with tumor cell lysate or killed tumor cells and found that irradiated lung tumor cells as a source of tumor antigen for DC loading is superior to tumor cell lysate or killed tumor cells in efficient induction of antigen-specific T-cell responses. Our results demonstrate the feasibility of using lung tumor cell-loaded DC to induce immune responses against lung cancer-associated antigens and support ongoing efforts to develop a DC-based lung cancer vaccine.

Adenocarcinoma↗
PubMed2003

Technology evaluation: bevacizumab, Genentech/Roche.

Bevacizumab, an antivascular endothelial growth factor monoclonal antibody, is being developed by Genentech and Roche as an anti-angiogenesis therapy for the potential treatment of solid tumors. In June 2003, bevacizumab was granted Fast Track status by the FDA for the potential treatment of first-line colorectal cancer. The antibody is currently in phase III trials for non-small-cell lung, colorectal and breast cancers, and in phase II trials for various other solid tumor types.

Angiogenesis Inhibitors↗
PubMed2002

Serological cloning of PARIS-1: a new TBC domain-containing, immunogenic tumor antigen from a prostate cancer cell line.

Identifying immunogenic tumor antigens plays a critical role in developing efficient diagnostic and therapeutic strategies for treatment of cancer. Using a recently developed technology, serological identification of antigens by recombinant expression cloning (SEREX), we identified a total of 8 genes whose expression elicited antibody responses in prostate cancer patients. Of the 8 genes, 5 represented known genes in the GenBank database, 2 were previously uncharacterized genes, and 1 showed sequence homology to a mouse gene. The sequence feature and the expression of one of the novel genes, prostate antigen recognized and identified by SEREX (PARIS-1), are determined in this study. The PARIS-1 cDNA is 3257 bp in length and contains a complete open reading frame of 2751 bp encoding for a primary translation product of 917 amino acids. Using Northern blot hybridization assay, we detected a single species of approximately 3.3 kb PARIS-1 mRNA that is differentially expressed in prostate normal and cancer cells. Western blot analysis confirmed the expression of the PARIS-1 protein in these cells. Structure analysis revealed that PARIS-1 protein contains a TBC domain that is conserved in the family of cell cycle-regulatory and Rab GTPase-activating proteins (Rab-GAP). Thus, the PARIS-1 protein may play a role in regulation of cell differentiation and growth or represent a new member of the Rab-GAP family.

Amino Acid Sequence↗
PubMed2002

The development of immunotherapies for non-small cell lung cancer.

Standard of care for non-small cell lung cancer (NSCLC) (surgery, chemotherapy and radiation) may enhance patient survival but the enhancement is typically transient and quite uncommon with advanced disease. Researchers and medical professionals are using new approaches to improve patient mortality and morbidity. One of these approaches, immunotherapy, seeks to stimulate antitumour immunity above a threshold level needed for tumour regression or to induce stability in the face of progression. Among the most established approaches are vaccines involving monoclonal antibodies (mAbs) or immune effector cells. These approaches stimulate the humoral and cell-mediated arms of the immune system, respectively. As the development of humanised or fully human antibodies has spurred exploration of radioimmunoconjugates and immunotoxins, mAbs have enjoyed a revival of sorts. Cell-based therapies using the tumour cell itself as a vaccine component has resulted in disease stabilisation or regression. In addition, immune cells (e.g., T-lymphocytes and dendritic cells [DCs]) are the focal point of numerous patient trials in which meaningful clinical impact was achieved. In general, there are many tactics under development for the treatment of NSCLC. This review primarily concerns immunotherapeutic cancer treatments that are either already in clinical trial or well progressed into preclinical studies.

Animals↗
PubMedDate not supplied

Current methods for loading dendritic cells with tumor antigen for the induction of antitumor immunity.

The immunotherapy of cancer is predicated on the belief that it is possible to generate a clinically meaningful antitumor response that provides patient benefit, such as improvement in the time to progression or survival. Indeed, immunotherapeutics with dendritic cells (DC) as antigen-presenting delivery vehicles for cell-based vaccines have already improved patient outcome against a wide range of tumor types (1-9). This approach stimulates the patient's own antitumor immunity through the induction or enhancement of T-cell immunity. It is generally believed that the activity of cytotoxic T lymphocytes (CTL), the cells directly responsible for killing the tumor cells in vivo, are directed by DC. Therefore, the goal of many current designs for DC-based vaccines is to induce strong tumor-specific CTL responses in patients with cancer. In practice, most studies for DC-based cancer vaccine development have focused on the development of methods that can effectively deliver exogenous tumor antigens to DC for cross-priming of CD8+ T cells through the endogenous MHC class I processing and presentation pathway (10). To date, many methods have been developed or evaluated for the delivery of defined and undefined tumor antigens to DC. This review provides a brief summary on these methods, the techniques used in these methods, as well as the advantages and disadvantages of each method.

Animals↗