The Third Annual Tregitope Update Meeting took place in Providence, RI on May 11, 2011. The meeting was co-organized by the URI Institute for Immunology and Informatics (iCubed) and EpiVax and followed the very successful Immunogenicity: Determinants and Correlates conference. The meeting was attended by 45 local, national, and international researchers. The following oral reports were presented: “Tregitope Overview, History, and Status” by A. De Groot (EpiVax), “Tregitopes: Mechanisms and Delivery” by L. Cousens (EpiVax), “Alloimmunity and Transplant Tolerance” by N. Najafian (Harvard Brigham and Womens’ Hospital), “Immune Responses in AAV-Mediated Gene Transfer” by F. Mingozzi (Childrens’ Hospital of Philadelphia), “Tregitopes, T Helper Cells, and EAE” by Wassim Elyaman (Harvard Brigham and Womens’ Hospital). A plenary session presentation by Dr. David Scott pointed to the close parallels between the mechanisms of action of Tregitope and similar findings for IVIG ([i]).
Feedback from the audience was positive and discussion on mechanisms of action and future therapeutic applications was enthusiastic.
Highlights of the meeting included:
Tregitope Mechanism of Action. Leslie Cousens (EpiVax) presented new data on APC modulation in humans and mice. Co-incubation of Tregitope with PBMC (human and mouse) leads to downregulation of CD80, CD86, and MHC class II at 72 hours; IT3 is increased.
Transplantation Tolerance. Ciara Magee and Nader Najafian showed the impact of Tregitope on transplantation. Tregitope treatment supported successful cardiac transplant from a Balb/C into a CD28K0 CD57Bl/6 mouse (in the majority of mice, >100 days). The Tregitope effect on gamma interferon and IL-10 secretion varied under a wide range of conditions (Th1, Th2, Th17 and Treg) which may explain its pleiotrophic effects in different models. Dr. McGee’s work received a young investigator award at ATC 2011.
Gene therapy. Exciting work by Mingozzi et al. pointed to a new mechanism for Treg control of immune responses, similar to the T-cell-to-T-cell regulation described by Allan and Hafler ([ii]). Dr. Mingozzi and colleagues at CHOP are exploring applications in which Tregitopes that are covalently linked or fused to the target epitope or antigen.
Multiple Sclerosis model (EAE). Wassim Elyaman presented evidence that Tregitope effects are closely paralleled by IVIG, in the EAE model system. The role of IL-9 and the effect of Tregitopes on dendritic cell phenotype was described.
Cousens, L and De Groot A. Regulating Immune Response to Biologics with Tregitopes, A Paradigm-Shifting Solution? 2011 AAPS National Biotechnology Conference, Invited oral presentation, Session 191 Immune Tolerance Induction, May, 2011.
De Groot, AS, Najafian, N, Hui, DJ, Mingozzi, F, Cousens, LP, Moise, L, Scott, DW, Khoury, S, Elayman, W, and Martin, W. Making Better Biologics by Harnessing Tolerance and Immunogenicity. 2011 AAPS National Biotechnology Conference, May, 2011.
Cousens, LP, DuPont, R, Levitz, L, Martin, WD, and De Groot, AS. Development of In Vitro Methods for Monitoring Tregitope Efficiency. First Immunogenicity: Determinants and Correlates Conference, Providence, RI, Poster presentation, May, 2011.
Cousens, LP, Levitz, L, DuPont, R, Martin, WD, and De Groot, AS. Tregitope Mechanism of Action at the Immunological Synapse. First Immunogenicity: Determinants and Correlates Conference, Providence, RI, Poster presentation, May, 2011.
Cousens, LP, Moise, L, Martin, WD, DuPont, R, Martin, BA, and De Groot, AS. Designing the optimal delivery vehicle for Regulatory T Cell Epitopes, “Tregitopes”. First Immunogenicity: Determinants and Correlates Conference, Providence, RI, Poster, May, 2011.
De Groot, AS, and Tregitope PPG collaborators. Tregitopes and tolerance: Harnessing regulatory T cells to suppress inflammation. Tenth World Congress on Inflammation, accepted for oral presentation, June 2011.
[i]. Kaufman GN, Massoud AH, Audusseau S, Banville-Langelier AA, Wang Y, Guay J, Garellek JA, Mourad W, Piccirillo CA, McCusker C, Mazer BD. IVIG attenuates airway hyperresponsiveness in a murine model of allergic asthma. Clin Exp Allergy. 2011 May;41(5):718.
[ii]. Baecher-Allan, C and Halfer, DA. Human regulatory T cells and their role in autoimmune disease. Immunol. Rev. 2006; 212:203-216.