Lecture will be held in English

Hosted by

Michaela Fojtů

About the lecture

Harnessing Nanoscale Communication for Next-Generation Anticancer Therapy

Communication by cancer cells is one of the key factors associated with disease progression, immune evasion, metastasis, and drug resistance. Cancer cells communicate with the tumor microenvironment and its neighboring cells for transferring ions, metabolites, growth factors, and cell organelles by a variety of mechanism, which includes exosomal, paracrine, and direct physical communication. Cancer cells communicate with immune cells through specific extracellular proteins, known as immune checkpoints, to send kill-me-not signals to T cells and macrophages. The use of monoclonal antibodies to block these immune checkpoint-based communications, known as immunotherapy, has made a paradigm shift in anticancer therapy in the last decade (Nobel Prize in Medicine 2018). However, poor therapeutic efficacy has been observed in the majority of cancer patients. Recently, we have investigated a novel mechanism of immune evasion by cancer cells through a nanoscale physical communication with immune cells. We have observed that cancer cells use nanoscale connections, known as tunneling nanotubes, to hijack mitochondria from T cells. The transfer of mitochondria metabolically empowers the cancer cells and increases their proliferation, metastasis, and drug resistance. In contrast, the T cell population depletes because of metabolic deactivation. Blocking the nanotube-mediated mitochondria transfer by pharmacological inhibitor has shown potential therapeutic implications in increasing intrinsic T cell immune response and elevating the therapeutic efficacy in combination with traditional immunotherapy. To integrate the pharmacological inhibitor and immune checkpoint inhibitors in a single platform, we have introduced antibody-conjugated drug-loaded nanotherapeutics (ADN), which can block immune checkpoints and can deliver pharmacological drugs selectively to the tumor. These immune-engineered nanotherapeutics can offer increased antitumor efficacy by activating adaptive as well as innate immunity and inhibiting the molecular driver for cancer cell survival. It has shown increased therapeutic efficacy in the syngeneic lung and breast cancer mice model, which is not responsive to traditional immunotherapy and monotherapies. Hence, a mechanistic understanding of cellular communication is critical to introduce novel therapeutic strategies for increasing treatment modality in cancer.

Registration for lunch with the speaker /for Ph.D. students/

The sponsored lunch usually takes place in the Campus River restaurant. Please meet the speaker and other students at 12:45 at the reception desk at the main entrance (building B22, see the map below).