Available Technology
Naturally occurring molecule serves as a novel adjuvant to boost immune responses
Technology:
Novel methods for inducing antigen specific tolerance
Markets Addressed
Immunostimulation: The previously unknown role for this naturally occurring molecule may be used to develop a novel vaccine adjuvant to strongly stimulate immune responses.
Induction of antigen specific tolerance: Immunosuppressive agents are commonly used in a variety of clinical settings, leading to broad therapeutic opportunities for this technology. Immunosuppression is a crucial part of many medical procedures such as transplantation, and is used to treat a range of inflammatory and autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, psoriasis and lupus.
The majority of approved immunosuppressive agents act non-specifically to inhibit immune inflammatory activity. Not only do these drugs produce numerous side effects, they are only partially effective in inhibiting self-reactive immune cell function. Antigen-specific therapies may offer significant advantages by selectively blocking the effects of self-reactive immune cell function, while maintaining the ability of the immune system to remove non-self antigens.
Innovations and Advantages
Dendritic cells (DCs) are a type of immune cell that capture antigens in peripheral tissues and travel to the local lymph nodes where they activate antigen-specific T- and B-cells by presenting the antigens on their surfaces. Once activated, naïve CD4+ T-cells proliferate and can differentiate into effector T-cells and memory T-cells which usually exert immune functions that lead to the elimination of the offending antigen.
Alternatively, CD4+ T-cells can differentiate into regulatory T-cells (Treg) which suppress the activity of other immune cells in order to maintain immune homeostasis and tolerance to self-antigens. One class of Tregs, naturally occurring Tregs (nTreg), arises in the thymus and is characterized by the co-expression of Foxp3 transcription factor and IL-2 receptor alpha chain (CD25). Adaptive Tregs (aTregs) can also arise in non-inflammatory situations by conversion of conventional CD4+ T-cells, which suppress responses to common antigens, such as food or harmless components of the environment.
The von Andrian laboratory demonstrated that a naturally occurring molecule can serve as a novel adjuvant to boost immune responses, a role previously unknown for this molecule. Further, inhibition of a specific receptor for this molecule, as well as other key factors in that receptor's signaling pathway, can induce tolerogenic DC that convert conventional CD4+ T-cells to aTregs and promote antigen specific tolerance.
• Immunostimulation using novel adjuvant
The lab identified a naturally occurring molecule that can serve as an adjuvant to boost the immunostimulatory function of DC. DCs treated with this molecule induced more robust T-cell proliferation than adjuvants that act on Toll-like receptors, such as LPS and CpG. This molecule may therefore be used to develop a novel adjuvant for the induction of strong immune responses.
• Induction of tolerogenic DC and antigen specific tolerance
o Induction of tolerogenic DC: Inhibition of a DC-expressed receptor for this naturally occurring molecule significantly boosts the tolerogenic capacity of DC. Researchers treated DCs with an inhibitor of the molecule’s signaling pathway, and then cultured them with naïve CD4+ T-cells. This treatment induced the differentiation of Foxp3-expressing aTregs more robustly than DCs treated with other cocktails known to induce Foxp3 expression. Blocking this pathway may therefore be effective in suppressing immune responses.
o Induction of antigen specific tolerance: Researchers in the lab also discovered novel methods of transforming naïve human CD4+ T-cells into aTregs. Although aTregs have been extensively characterized in rodents, it was previously impossible to artificially induce them in humans using naïve T cells as precursors. DCs treated with key factors and cultured with naïve CD4+ T-cells produced aTregs that expressed molecular markers characteristic of the naturally occurring Tregs, such as Foxp3 and CD25.
They further demonstrated in vivo activity of the artificially induced tolerogenic DCs. DCs treated with these key factors were injected into mice suffering from Experimental Allergic Encephalomyelitis, a model of brain inflammation, and shown to not only block the progression of the disease but also reverse existing neuropathology.
Additional Information
Intellectual Property Status: This technology is available for worldwide, exclusive licensing and/or a collaborative research program with the von Andrian laboratory.
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Inventor(s):
Maldonado, Roberto A.
Vascotto, Fulvia
von Andrian, Ulrich H.
Categories:
For further information, please contact:
Michal Preminger, Director of Business Development
(617) 432-0920
Reference Harvard Case #3599