If you want to hear about Tregitope join us (for free) in Boston on May 16th, at the Westin Copley. Email Shannon Pelletier spelletier@epivax.com and we’ll reserve your seat.
The discovery of natural regulatory T cell epitopes in the sequence of therapeutic mAbs represents a paradigm shift for protein therapeutics, allergy, autoimmunity and transplantation. These natural Treg epitopes (also known as Tregitopes) are promiscuous MHC Class II T cell epitopes located in the Fc and framework regions. At a meeting scheduled for May 16th, 2010, the latest Tregitope research will be reviewed, and protocols will be refined. Members from five collaborating laboraories will be present.
The Tregitopes have been evaluated in vitro and in vivo in five collaborating laboratories who will be speaking at the Tregitope meeting. Investigations in allergy (OVA model), transplantation (MLR, cardiac transplant model), protein therapeutics (OVA, FVIII) and autoimmunity (EAE, NOD) have demonstrated that tolerance to a range of antigens can be induced by co-administration of the Tregitopes with the target antigens.
Tetramer staining confirms that Tregitopes specifically activate CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). In vitro, co-incubation of antigens with “Tregitopes” in vitro leads to suppression of effector cytokine and chemokine secretion, reduced proliferation of effector T cells, and expansion of antigen-specific adaptive Tregs (aTregs). In vivo, co-administration of Tregitopes with a range of proteins (such as FVIII, thyroid stimulating hormone receptor, ovalbumin, and autoantigens) leads to suppression of T cell and antibody responses to the test antigens. Differences in the Tregitope content of monoclonal therapeutics such as ofatumumab and rituximab, humira and infliximab, explain differences observed in the clinical setting.
The talks at this session will describe recent laboratory studies and conclude with a discussion of the role of Tregitopes in the design of safer, more effective protein therapeutics, whether these proteins are monoclonal antibodies, novel scaffolds, replacement therapies or biosimilars. The therapeutic implications for the fields of allergy, autoimmunity and transplantation will also be described. Regulatory T cell induction in the context of protein therapy and inflammation may contribute to the design of improved biologic therapeutics for a wide range of clinical conditions.