Standard therapies for many common cancers remain toxic and are often ineffective. Cellular immunotherapy has the potential to be a highly targeted alternative, with low toxicity to normal tissues but a high capacity to eradicate tumor. In this chapter we describe approaches that generate cellular therapies using active immunization with cells, proteins, peptides, or nucleic acids, as well as efforts that use adoptive transfer of effector cells that directly target antigens on malignant cells. Many of these approaches are proving successful in hematologic malignancy and in melanoma. In this chapter we discuss the advantages and limitations of each and how over the next decade investigators will attempt to broaden their reach, increase their efficacy, and simplify their application.
[Show abstract][Hide abstract] ABSTRACT: The problem of formulating plans under uncertainty and coping with dynamic decision problems is a major task of both artificial intelligence and control theory applications in medicine. In this paper we will describe a software package, called DT-Planner, designed to represent and solve dynamic decision problems that can be modelled as Markov decision processes, by exploiting a novel graphical formalism, called influence view. An influence view is a directed acyclic graph that depicts the probabilistic relationships between the problem state variables in a generic time transition; additional variables, called event variables, may be added, in order to describe the conditional independencies between state variables. By using the specified conditional independence structure, an influence view may allow a parsimonious specification of a Markov decision process. DT-Planner lets the user specify and manage models through a user-friendly graphical interface, and implements efficient for policy determination algorithms. DT-Planner is written in C with Open Interface libraries and can be obtained, for non commercial use, via anonymous ftp without charge.
Computer Methods and Programs in Biomedicine 12/1997; 54(3):183-200. DOI:10.1016/S0169-2607(97)00044-8 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The graft-versus-leukemia effect of allogeneic blood or marrow transplantation is a dramatic example of the power of the immune system to eradicate malignant disease. In this personal essay, adapted from the inaugural Mortimer M. Bortin Lecture presented at the 2004 Tandem BMT Meetings, the author recounts early efforts by Bortin and others to manipulate the graft-versus-leukemia effect and separate it from the potentially fatal complications of graft-versus-host disease. (C) 2004 American Society for Blood and Marrow Transplantation.
Biology of Blood and Marrow Transplantation 09/2004; 10(8):505-23. DOI:10.1016/j.bbmt.2004.05.005 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The immunoglobulin molecule contains structural features that make it a powerful tool for cancer therapy (eg, an extremely high specificity and binding affinity for the target molecule that results in low toxicity). Several approaches have been used: monoclonal antibodies targeting a ligand (eg, bevacizumab, anti-vascular endothelial growth factor), monoclonal antibodies targeting a receptor (eg, cetuximab, anti-epidermal growth factor receptor), vaccines targeting a ligand (eg, G17DT, anti-gastrin), or a cell surface antigen (eg, carcinoembryonic antigen-TRIad of COstimulatory Molecules, anti-CEA). Another approach attempts to harness the cellular arm of the immune response (ie, cytotoxic T cells, natural killer cells) for specific killing of tumor cells. The putative underlying mechanism of antibody strategy is the inhibition of intracellular signaling pathways and induction of apoptosis. Clinical evidence suggests that while most of these antibodies achieve limited antitumor activity as monotherapy, they are significantly more efficacious than single agents when combined with chemotherapy. Future use of these agents will include optimized combination chemotherapy/immunotherapy regimens as well as monoclonal antibodies conjugated to cytotoxic molecules and radionuclides.
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