MMD Materclass

MMD mini-symposium: Chemical Immunology

28 September 2017 14:00 hrs. - 18:00 hrs.
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
MMD mini-symposium: Chemical Immunology

Carl Figdor / Martijn Verdoes, Dept. of Tumor Immunology, RIMLS

28-09-2017 14:00:0028-09-2017 18:00:00Europe/AmsterdamMMD mini-symposium: Chemical Immunology Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route

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14:00-15:00: Patrick Beusker, Synthon Biopharmaceuticals, Nijmegen (will substitute Marco Timmers)
Antibody-drug conjugates – Trojan horses in oncology.

undefinedAntibody-drug conjugates (ADCs) are designed to combine the specificity of antibodies directed against tumor-associated targets with potent cytotoxicity. Upon internalization of the ADC, the antibody-bound cytotoxic payload is released intracellularly, leading to programmed tumor cell death.
While the cytotoxic payloads used in the majority of advanced programs in the field prevent tubulin polymerization during cell division, Synthon's differentiated linker-drug technology - applying valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA) - is based on synthetic duocarmycin analogs, which bind to the minor groove of DNA and subsequently cause irreversible alkylation of the DNA. This disrupts the nucleic acid architecture, which induces tumor cell death.
Synthon’s lead ADC program trastuzumab duocarmazine (SYD985), a novel generation duocarmycin-based HER2-targeting ADC in Phase III clinical development, exhibits a favorable therapeutic window and shows impressive anti-tumor activity in various HER2-expressing cancer types, including metastatic breast cancer and metastatic bladder cancer.
This presentation will focus on the design of Synthon’s linker-payload technology and the differentiating features compared to other ADCs in preclinical models and clinical studies.

​15:00-16:00: Mustafa Diken, Institute for Translational Oncology, Mainz
The evolution of RNA-based vaccines against cancer.

undefinedImmunotherapy has evolved as a promising alternative to conventional treatments against cancer. Thanks to its unique characteristics, mRNA can act not only as a source for antigen but also as an adjuvant for activation of the immune system. Vaccination with tumor antigen-coding RNA has been shown to be capable of efficiently inducing T cell responses and anti-tumor immunity in preclinical models and RNA-based vaccines are currently being tested in clinical trials with promising results. This lecture will summarize the evolution of RNA-based vaccines against cancer with a special focus on advancements enabling systemic delivery of RNA as well as personalized cancer vaccines.

16:00-17:00: Celia Berkers, Utrecht University
Finding the metabolic Achilles′ heel of T cells.

undefinedIn a healthy immune response there is a dynamic balance between opposing activities of two T cell types: conventional T cells (Tconv) and regulatory T cells (Treg). In contrast, immune related diseases are often characterized by a disbalance between these cell types. Regulatory CD4 T cells (Treg) inhibit the response of conventional CD4 and CD8 T cells (Tconv) to self- and foreign antigens. Treg are critical to inhibit autoimmunity. Patients with autoimmune diseases such as rheumatoid arthritis will likely benefit from Treg stimulation. On the other hand, Treg impede anti-tumor immunity and therefore, cancer patients will likely benefit from Treg inhibition. But because Treg and Tconv share many features - including costimulatory and cytokine receptors - compounds that selectively modulate different T cell types are scarce. One aspect in which Treg may differ significantly from Tconv is in their metabolic features. Upon activation in lymphoid organs, T cells proliferate extremely fast and this places unique demands on their metabolism. But whereas proliferation of Tconv is depending on the mTORC1 pathway, Treg proliferation is not. Therefore, we aim to map the metabolic differences between Treg and Tconv using a metabolomics approach. To this end, we use state-of-the-art LC/MS and combine steady-state metabolomics screens with metabolic flux studies using stable isotope-labelled nutrients. By studying not only in vitro expanded T cells but also freshly isolated primary human T cell populations, we now start to see different metabolic signatures in Treg and Tconv, especially during activation. Further exploration of these differences may aid in the identification of novel targets that can be exploited to selectively modulate T cell activity.

17:00-18:00 Drinks and informal discussions.

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