Podcast
Questions and Answers
What was a crucial stepstone in the progress of adoptive cell therapies?
What was a crucial stepstone in the progress of adoptive cell therapies?
- The discovery of Graft-versus-Host Disease
- The authorization of Kymriah by the FDA in 2017 (correct)
- The approval of five more CAR-T therapies
- The development of non-viral transfection technologies
What is a major advantage of Natural Killer cells over CAR-T cell therapies?
What is a major advantage of Natural Killer cells over CAR-T cell therapies?
- They avoid severe side-effects such as GvHD and CRS (correct)
- They are associated with more severe side-effects
- They are more effective in treating solid tumors
- They are easier to genetically modify
What is a limitation of using viral vectors for NK cell modification?
What is a limitation of using viral vectors for NK cell modification?
- They require a lengthy and expensive product development process (correct)
- They are not effective in treating hematological malignancies
- They can only be used for T-cells
- They are too expensive to develop
What is the goal of non-viral transfection technologies?
What is the goal of non-viral transfection technologies?
Why are non-viral transfection technologies being developed?
Why are non-viral transfection technologies being developed?
What is the focus of the review mentioned in the text?
What is the focus of the review mentioned in the text?
What is the primary function of natural killer cells in immunosurveillance?
What is the primary function of natural killer cells in immunosurveillance?
What is the primary difference between the activation mechanisms of CD8+ T cells and natural killer cells?
What is the primary difference between the activation mechanisms of CD8+ T cells and natural killer cells?
What is the role of inhibitory receptors such as KIR and NKG2A on natural killer cells?
What is the role of inhibitory receptors such as KIR and NKG2A on natural killer cells?
What is the purpose of the balance between activating and inhibitory signals in natural killer cells?
What is the purpose of the balance between activating and inhibitory signals in natural killer cells?
What is the effect of interferon γ (IFN-γ) produced by activated natural killer cells?
What is the effect of interferon γ (IFN-γ) produced by activated natural killer cells?
What is the consequence of a mismatch in HLA typing during allogenic therapy?
What is the consequence of a mismatch in HLA typing during allogenic therapy?
Study Notes
Adoptive Cell Therapies
- Kymriah (tisagenlecleucel) was authorized by the FDA in 2017, marking a crucial step forward in treating blood cancers.
- Five more CAR-T therapies have been approved for the treatment of hematological malignancies since then.
Limitations of CAR-T Cell Therapies
- CAR-T cell therapies are associated with severe side-effects such as Graft-versus-Host Disease (GvHD), cytokine release syndrome (CRS), and neurotoxicity.
Natural Killer (NK) Cells
- NK cells are innate, cytotoxic lymphocytes that contribute to immunosurveillance by identifying and killing virally infected cells and tumor cells.
- NK cells can be genetically modified to improve their therapeutic efficacy in various ways.
- Viral transduction of NK cells remains inefficient and induces cytotoxic effects.
Non-Viral Transfection Technologies
- Non-viral transfection technologies are being developed to address the shortcomings of viral vectors.
- These technologies aim to engineer NK cells for cancer immunotherapies.
Mechanism of NK Cells
- NK cells do not rely on antigen-specific receptors for their activation.
- Their activation depends on the integration of signals derived from inhibitory and activating receptors expressed on their surface.
- Inhibitory receptors such as Killing Inhibitory Receptor (KIR) and NKG2A can interact with MHC-associated molecules and inhibit NK cell activation.
- Activating receptors such as NKG2D, Natural Cytotoxicity Receptors (NCRs), and DNAM-1 can result in NK cell activation upon interaction with tumor ligands.
Cytotoxicity and Immune Response
- NK cells can mediate cytotoxicity immediately upon interaction with the target cell.
- Upon activation, they release cytolytic granules and cytotoxic cytokines such as interferon γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
- These chemokines and cytokines influence an array of immune cells, including B and T cells, macrophages, neutrophils, and dendritic cells.
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Description
Learn about the developments in CAR-T cell therapies, approved treatments, and associated side-effects in the treatment of blood cancers.
