Naslov
A Human Monoclonal Antibody and Antigen Discovery Platform Based on Allogeneic Hematopoietic Stem Cell Transplantation and Phage Display

Autori
Baskar, Sivasubramanian ; Levy, Jessica M ; Samija, Ivan ; Pavletic, Steven Z ; Bishop, Michael R ; Rader, Christoph

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Cancer Immunology & Immunotherapy: Realizing the Promise / Rosenberg, Steven A - Bethesda (MD), 2008, 79-79

Skup
Cancer Immunology & Immunotherapy: Realizing the Promise

Mjesto i datum
Bethesda (MD), Sjedinjene Američke Države, 11.09.2008. - 12.09.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
chronic lymphocitic leukemia; allogeneic hematopoietic stem cell transplantation; phage display; human monoclonal antibody therapy

Sažetak
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently the only curative treatment available for patients with hematologic malignancies such as B-cell chronic lymphocytic leukemia (B-CLL). Both the graft versus tumor (GVT) activity, and its counterpart graft-versus-host-disease (GVHD), are believed to be mediated primarily by alloreactive donor T cells. Shifting the focus to another component of the adaptive immune system, we are investigating whether alloHSCT-induced antibodies derived from donor B cells may also have a role in GVT activity. In addition, these antibodies may serve as tools for the discovery of new antigens for human monoclonal antibody (mAb) therapy. Using quantum dot technology and multiparameter flow cytometry, we established a sensitive assay for the detection of post-alloHSCT serum antibodies against cell surface antigens. Post-alloHSCT sera collected from B-CLL patients at defined time points after transplantation showed significant binding to B-CLL tumor cells but not normal B cells. Pre-alloHSCT sera, donor sera, and control sera were negative. In order to identify post-alloHSCT serum antibodies and subsequently the cell surface antigens they recognize, we generated a human Fab library from post-alloHSCT peripheral blood mononuclear cells (PBMC) and selected it on B-CLL tumor cells by phage display. A panel of human Fab-phage with B-CLL tumor cell reactivity was strongly enriched over three rounds of selection. One clone, designated JML-1, was expressed and purified as fully human IgG1 and analyzed for binding to B-CLL tumor cells from untreated patients as well as to PBMC subpopulations from healthy donors. These analyses suggested that the antigen recognized by JML-1 is restricted to B cells and overexpressed in B-CLL tumor cells. JML-1 IgG1 is anticipated to facilitate the discovery of relevant antigen and, at the same time, provide a fully human format for mAb therapy of B-CLL and possibly other B-cell malignancies.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

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