Biomedical subjects

A A Eggert

Publications and source records attributed to A A Eggert.

17 recordsLinked to original sources

PubMed2000

Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model.

Tyrosinase-related protein (TRP) 2 belongs to the melanocyte differentiation antigens and has been implicated as a target for immunotherapy of human as well as murine melanoma. In the current report, we explored the efficacy of nonmutated epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated, tumor-reactive immunity in vivo within the established B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived epitopes for vaccination provides a mouse model that closely mimics human melanoma without introduction of xenogeneic or otherwise foreign antigen. The results demonstrate that vaccination with TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the peptides used for vaccination. In contrast, within this autologous model, vaccination with TRP2 peptide in Freund's adjuvant or TRP2-encoding plasmid DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based vaccines to induce immunity against autologous tumor-associated antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.

Amino Acid Sequence↗

PubMed2000

Dendritic cell-based vaccines: from mouse models to clinical cancer immunotherapy.

B and T lymphocytes are the effectors of specific immunity. However, their function is critically dependent on dendritic cells (DC). DC are professional antigen presenting cells that both initiate and modulate the immune response. The recent breakthrough in the generation of DC from their progenitors has stimulated research on DC in both fundamental and clinical immunology. Objective immune response induction has now been reported in clinical studies using DC. In this review we discuss the development and potential of DC-based vaccines to induce antitumor immunity.

Animals↗

PubMed2000

The LIS as process manager. Save money and reduce tech fatigue.

Explore the source record for details and available documents.

Autoanalysis↗

PubMed1999

Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration.

Dendritic cells (DCs) are professional antigen-presenting cells, well equipped to initiate an immune response. Currently, tumor antigen-derived peptide loaded DCs are used in clinical vaccination in cancer patients. However, the optimal dose and route of administration of a DC vaccine still remain to be determined. Using indium-111-labeled DCs, we investigated whether the route of administration does affect the biodistribution of DCs in lymphoid organs and whether it influences the outcome of DC vaccination in the B16 mouse melanoma tumor model. The results demonstrate that i.v. injected DCs mainly accumulate in the spleen, whereas s.c. injected DCs preferentially home to the T-cell areas of the draining lymph nodes. Using tyrosinase-related protein-2-derived peptide-loaded DC vaccination in a fully autologous B16 melanoma tumor model, we observed a delay in tumor growth, improved survival as well as increased antitumor cytotoxic T-cell reactivity after s.c. vaccination as compared to i.v. vaccination. These data demonstrate that optimal induction of antitumor reactivity against the autologous melanocyte differentiation antigen tyrosinase-related protein-2-derived peptide occurs after s.c. vaccination and correlates with the preferential accumulation of DCs in the T-cell areas of lymph nodes.

Animals↗

PubMed1999

Generation and functional characterization of mouse monocyte-derived dendritic cells.

Dendritic cells (DC) are potent antigen-presenting cells with the unique capacity to initiate primary immune responses. As a result, DC are currently used in clinical studies to induce immunity against infectious disease and malignant cells. However, multiple DC subsets exist and it has been suggested that the type of DC may affect the immune response induced. The vast majority of DC used in experimental mouse tumor models is derived from bone marrow progenitors. In contrast, most in vitro as well as in vivo human studies involve the use of DC generated from adherent peripheral blood-derived monocytes in the presence of GM-CSF and IL-4. In the current report, we describe for the first time the generation and characterization of mouse monocyte-derived DC (MODC). The results indicate that mouse MODC display similar morphology, phenotype and immunostimulatory activity as compared to bone marrow-derived DC. Both DC subsets were able to efficiently take up and subsequently cross-present protein antigen to cytotoxic T cells. Moreover, we demonstrate that vaccination with peptide-loaded MODC mediates induction of tumor-reactive immunity in vivo. The isolation and characterization of mouse MODC will provide a valuable research tool to investigate fundamental aspects of DC biology and which DC subsets are most suitable to induce anti-tumor immunity.

Adjuvants, Immunologic↗

PubMed1999

An overhead specimen handling system for variable workloads.

This unique overhead specimen handling system requires virtually no floor space and only a minimal amount of bench space. It uses state-of-the-art conveyors suspended near the ceiling to transport, log-in and sort blood specimens in standard specimen containers. Specimens placed into the system at bench-level bins are automatically singulated and loaded onto cleated conveyors and lifted to the main conveyor belt near the ceiling. The barcoded labels are then read as the containers are rotated under an optical scanner. The specimens are then diverted to the appropriate branch conveyor and lowered back to the bench level by cleated conveyors. The specimen handling system is rapid and accurate, requires no special containers, allows laboratorians to move unimpeded below it, and is inexpensive by automation standards. Studies show no adverse effect upon the specimens.

Automation↗

PubMed1998

The combination of specimen tracking with an advanced AutoLog in a laboratory information system.

The ability to provide timely laboratory results is an important aspect of quality which must be continually monitored. In order to complete all testing before the maximum turnaround time requirements are exceeded, laboratorians need to have immediate and automatic access to the location of specimens and the status of tests ordered on each specimen. Any such automated approach must be able to monitor continually the status of work in progress, while simultaneously linking it to a specimen tracking (history) system that allows real-time tracing of the path of specimens through all laboratory operations. The authors have greatly advanced the capabilities of the AutoLog technology and have added to it a tracking system that captures specimen movement with minimum user assistance. This has been accomplished without the need to implement total process automation.

Automation↗

PubMed1995

LabLink--the key to multi-computer interfacing.

The growing complexity of computing environments requires creative solutions to prevent the gain in productivity promised by computing advances from being swallowed up by the necessity of moving information from one environment to another. LabLink is an interfacing tool for accomplishing such transfers in a clinical laboratory environment. It handles the automated data transfer among four systems, as well as providing substantial back-up capacity for critical operations when systems are down for saves or maintenance.

Blood Banks↗

PubMed1991

Migrating a clinical laboratory information system between technologies.

The technical revolution that has strongly driven events in the clinical laboratory for the last thirty years is now threatening to make obsolete what has become the central pillar of operation in many laboratories, the minicomputer-based laboratory information system. Some of its functions could easily be absorbed by the personal computers which are proliferating in the laboratory, but any single step leap between systems risks replacing order with chaos. Appropriate use of networking tools, together with essential software development, can provide a systematic migrational path for both the administrative and technical computer support from one environment to another without the trauma of a massive replacement step.