Biomedical subjects

Charles A Nicolette

Publications and source records attributed to Charles A Nicolette.

3 recordsLinked to original sources

PubMed2004

A high-throughput proteo-genomics method to identify antibody targets associated with malignant disease.

Identification of antibody targets associated with malignant disease is indispensable to developing passive and active antibody-based therapeutics or diagnostic agents. We have developed a novel technique combining Western blotting, genetic profiling, and mass spectroscopy that allows for the rapid and unambiguous identification of such antigens in a high-throughput manner. Herein, we demonstrate this technique, designated Ab SCAN, by deducing the known target of a monoclonal antibody and by identifying a new antigen that was observed to be the frequent target of humoral immune responses in prostate cancer patients. In both instances, a specific antigen emerged as the sole protein candidate. The newly identified antigen, mannose-6-phosphate/IGF II receptor, may be an important naturally immunogenic antigen involved in prostate cancer. The Ab SCAN technique is uniquely suited to the analysis of longitudinal serum samples from clinical studies and could be a powerful tool to correlate humoral immune responses directed against discreet antigens with clinical events.

Antibodies, Monoclonal↗

PubMed2003

The identification of clinically relevant markers and therapeutic targets.

The history of tumor biomarker discovery has been one of limited success. Population based screens are few and of limited clinical usefulness. Biomarkers that are able to segregate patients by diagnosis, prognosis and appropriate therapeutic selection are in great need and will be the basis of the clinical management in the future. This review sets out the challenges inherent in the field of tumor biomarker discovery and the tools that we are using to meet that challenge. It is now possible, using this suite of technologies, to discuss novel tumor biomarkers in terms of a pipeline rather than single unique events in research. The future of clinical oncology management will use markers such as those being identified via these techniques to improve patient care through better diagnosis and hopefully to achieve greater success in treatment by exploiting tumor markers as therapeutic targets.

Antineoplastic Agents↗

PubMed2002

Solid-phase epitope recovery: a high throughput method for antigen identification and epitope optimization.

Self tolerance to MHC class I-restricted nonmutated self Ags is a significant hurdle to effective cancer immunotherapy. Compelling evidence is emerging that altered peptide ligands can be far more immunogenic than their corresponding native epitopes; however, there is no way to reliably predict which modifications will lead to enhanced native epitope-specific immune responses. We reasoned that this limitation could be overcome by devising an empirical screen in which the nearly complete combinatorial spectrum of peptides of optimal length can be rapidly assayed for reactivity with a MHC class I-restricted cytotoxic T cell clone. This method, solid-phase epitope recovery, quantitatively ranks all reactive peptides in the library and allows selection of altered peptide ligands having desirable immunogenic properties of interest. In contrast to rationally designed MHC anchor-modified peptides, peptides identified by the present method are highly substituted in predicted TCR contact residues and can reliably activate and expand effector cell populations in vitro which lyse target cells presenting the wild-type epitope. We demonstrate that solid-phase epitope recovery peptides corresponding to a poorly immunogenic epitope of the melanoma Ag, gp100, can reliably induce wild-type peptide-specific CTL using normal donor T cells in vitro. Furthermore, these peptides can complement one another to induce these responses in an overwhelming majority of normal individuals in vitro. These data provide a rationale for the design of superior vaccines comprising a mixture of structurally diverse yet functionally convergent peptides.

Antigen Presentation↗