TNF-a is a pro-inflammatory cytokine that is overexpressed in diverse inflammatory states such as rheumatoid arthritis. Anti-TNF therapies, including monoclonal antibodies (Abs), have demonstrated remarkable success in management of arthritis and other chronic inflammatory diseases. The possibility to elicit autoAbs to TNF-a (beneficial autoimmunity) has been proposed as an immunotherapeutic approach to neutralize systemic TNF-a (1). Studies using a DNA vaccination strategy in rat adjuvant arthritis mapped several epitopes for natural anti-TNF-a autoAbs in the C-terminal portion of the sequence. We previously showed that aldehyde-tagged peptide conjugates representing immunogenic epitopes of toxic shock syndrome toxin–1, could induce anti-toxin neutralizing Abs without the need of potent adjuvants (2). In the present study, using a C-terminal TNF-a recombinant polypeptide, we followed a similar approach to generate neutralizing Abs against TNF-a in Lewis rats. Immunized rats showed less severe symptoms in the collagen induced arthritis ( CIA) model. 1. Dalum I. et. al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 1999. 17:666-669. 2. Bavoso A, Ostuni A, De Vendel J, Pollaro F, Armentano F, Knight T, Makker S. and A. Tramontano. Aldehyde modification of peptide immunogen enhances protein-reactive antibody response to toxic shock syndrome toxin-1. J Pept Sci 2006. 12:843-849.
Tumor Necrosis Factor-a Neutralizing Antibodies Induced by a Glycolaldehyde-Modified C- terminal Polypeptide.
OSTUNI, Angela;BAVOSO, Alfonso;BRACALELLO, Angelo;
2012-01-01
Abstract
TNF-a is a pro-inflammatory cytokine that is overexpressed in diverse inflammatory states such as rheumatoid arthritis. Anti-TNF therapies, including monoclonal antibodies (Abs), have demonstrated remarkable success in management of arthritis and other chronic inflammatory diseases. The possibility to elicit autoAbs to TNF-a (beneficial autoimmunity) has been proposed as an immunotherapeutic approach to neutralize systemic TNF-a (1). Studies using a DNA vaccination strategy in rat adjuvant arthritis mapped several epitopes for natural anti-TNF-a autoAbs in the C-terminal portion of the sequence. We previously showed that aldehyde-tagged peptide conjugates representing immunogenic epitopes of toxic shock syndrome toxin–1, could induce anti-toxin neutralizing Abs without the need of potent adjuvants (2). In the present study, using a C-terminal TNF-a recombinant polypeptide, we followed a similar approach to generate neutralizing Abs against TNF-a in Lewis rats. Immunized rats showed less severe symptoms in the collagen induced arthritis ( CIA) model. 1. Dalum I. et. al. Therapeutic antibodies elicited by immunization against TNF-alpha. Nat Biotechnol 1999. 17:666-669. 2. Bavoso A, Ostuni A, De Vendel J, Pollaro F, Armentano F, Knight T, Makker S. and A. Tramontano. Aldehyde modification of peptide immunogen enhances protein-reactive antibody response to toxic shock syndrome toxin-1. J Pept Sci 2006. 12:843-849.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
