Our Science

DC Hyperactivation

Why Is Our DC Hyperactivation Platform Unique?

We generate exceptional memory T and B cells that provide life-long immunity

This platform uses a new class of immunotherapy, called hyperactivators, which enhance the intelligence of dendritic cells (DCs) to generate T and B cell mediated immunity—for life.

Our hyperactivators unleash the power of inflammasome activation within live DCs

Our hyperactivators activate inflammasomes within living DCs to produce IL-1β, the key T cell memory signal. Prior therapies targeting DCs have failed to provide durable immunity. They either cannot stimulate the IL-1β signal, or they use inflammasome stimuli that kill DCs via pyroptosis. We are shifting this paradigm by unleashing
IL-1β signals from living DCs.

Our hyperactivators lead DCs to be in the right place, at the right time

Our hyperactivators are uniquely capable of stimulating DC migration to lymph nodes, where naïve and memory T cells are activated. While previous attempts to stimulate DC activities were poor inducers of migration, we ensure these apex immune regulators are in the right place and at the right time, to promote durable immunity.

We are antigen agnostic

This muti-purpose platform can
target a wide array of antigens ranging from known single antigens to a complex source of unidentified antigens. We are leading a new era of rapid and low-cost immunotherapies. We provide personalized immunotherapy that is available for all patients within days.

Dendritic Cell Hyperactivation

An ideal immunotherapy induces robust and durable T cells that treat the disease and protects the patient from the disease recurrence for life.

DCs that receive infection-like signals become active and upregulate 3 functions that are necessary for their interaction with T cells:
  1. Antigen presentation
  2. Co-stimulatory molecule expression
  3. Secretion of cytokines that activate T cells
However, these 3 signals are not sufficient to promote long-lived memory T cells.

DCs that receive an injury-like signal in addition to the infection-like signal become hyperactive1,2. Corner Therapeutics proprietary hyperactivating molecules add two critical functions to DCs.

Migration in high numbers to lymph nodes where they can interact with naïve and memory T cells4,5. Production of T cell memory cytokine IL-1β from viable DCs, by unleashing their inflammasome machinery.

These 5 signals are critical to promote long-lived memory T cells3,4.

IL-1β is critical in generating new long-lived memory T cells as well as reactivating existing memory T cells5,6. Corner’s ability to promote IL-1β release from viable hyperactive DCs allows the rapid expansion of existing memory T cells and the differentiation of new antigen-specific T cells that combat disease throughout the life of the patient5-9.

Our Vaccine Development Approach

A broad antigen portfolio maximizes the impact a therapy can have in patients.

Corner’s platform can use antigens ranging from complex to single neoantigens. Corner’s technology generates rapid and low-cost immunotherapies accessible to all patients.

PERSONALIZED VACCINE

Corner’s platform can impact a wide range of solid and liquid cancers.

OFF THE SHELF VACCINE

Corner’s technology can target infectious diseases.

Bibliography:
  1. Zanoni, I. et al. An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science (1979) 352, 1232–1236 (2016).
  2. Zhivaki, D. & Kagan, J. C. Innate immune detection of lipid oxidation as a threat assessment strategy. Nature Reviews Immunology Preprint at https://doi.org/10.1038/s41577-021-00618-8 (2021).
  3. Zhivaki, D. et al. Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity. CellReports 33, 108381 (2020).
  4. Zhivaki, D. & Kagan, J. C. NLRP3 inflammasomes that induce antitumor immunity. Trends Immunol (2021) doi:10.1016/j.it.2021.05.001.L
  5. Ben-Sasson, S. Z. et al. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med 210, 491–502 (2013).
  6. Lee, P.-H. et al. Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells. J Exp Med jem.20181218 (2019) doi:10.1084/jem.20181218.
  7. Ben-Sasson, S. Z., Wang, K., Cohen, J. & Paul, W. E. IL-1 Strikingly Enhances Antigen-Driven CD4 and CD8 T-Cell Responses. Cold Spring Harb Symp Quant Biol 78, 117–124 (2013).
  8. Ben-Sasson, S. Z. et al. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A 106, 7119–24 (2009).
  9. Jain, A., Song, R., Wakeland, E. K. & Pasare, C. T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells. Nat Commun 9, 1–13 (2018).
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