New gen therapeutics letsgooo Flashcards

Question

Trans-Amplifying mRNA | taRNA

Answer 1

An advancement of the saRNA platform. By separating the target mRNA to be amplified and the replicase encoding mRNA This makes the development of therapeutic mRNAs even more flexible, as the replicase can amplify mRNA encoding of not only one protein, but several different ones. taRNA system comes with the promise of easy, time- and cost-efficient manufacturing taRNA-based vaccine platform well suited and universally applicable for rapidly evolving pathogens as well as newly emerging infectious diseases.

Answer 2

refer to notes

Answer 3

Tailored reprogramming of autologous T cells from cancer patients to recognize and attack their tumors Retargeting of T cells can be achieved via introduction of tumor-specific receptors into patient-derived T cells. T cells are mostly engineered to express either T cell receptors, or TCRs, or chimeric antigen receptors, or CARs CAR expressing T cells, or CAR T cells, became the first engineered T cell therapy to obtain FDA approval for some B cell derived hematological malignancies.

Answer 4

A protective protein produced by the immune system in response to the presence of a foreign substance, called an antigen.

Answer 5

Antibody therapy involves giving antibodies that have been specially made in a laboratory to target an antigen on a cancer cell. Therapeutic antibody drugs are used for treating various human diseases, including many cancers.

Answer 6

Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system's attack on cancer cells.

Answer 7

They are designed to bind to antigens that are generally more numerous on the surface of cancer cells than healthy cells. Monoclonal antibodies, or mAbs, have transformed from scientific tools to powerful human therapeutics. In addition, identified antigen binding domains are also fundamental elements for the construction of novel therapeutic formats and formulations, such as CAR-T cells, bispecific therapeutics and targeted nanoparticles

Answer 8

ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal

Answer 9

Low immunogenicity High antigen binding activity high stability

Answer 10

Some monoclonal antibodies block the connection between a cancer cell and proteins that promote cell growth — an activity that is necessary for tumor growth and survival. Some even block protein-cell interactions necessary for the development of new blood vessels, hence preventing blood vessel growth.

Answer 11

Some immune system cells depend on antibodies to locate the target of an attack. Cancer cells that are coated in monoclonal antibodies may be more easily detected and targeted for destruction. Some monoclonal antibodies can trigger an immune system response that can destroy the outer wall (membrane) of a cancer cell.Rect2

Answer 12

Because of a monoclonal antibody's ability to connect with a cancer cell, the antibody can be engineered as a delivery vehicle for other treatments. When a monoclonal antibody is attached to a small radioactive particle, it transports the radiation treatment directly to cancer cells and may minimize the effect of radiation on healthy cells. This variation of standard radiation therapy for cancer is called radioimmunotherapy.

Answer 13

1. Developed and integrated multiple complementary antibody and antibody-mimetic protein technologies into our overall portfolio of treatment approaches 2. Multiple antibody discovery engines significantly expand our targeting repertoire and enable us to directly, rapidly and efficiently produce new mAb candidates 3. With the acquisition of MAB Discovery GmbH’s antibody generation unit in 2019, they integrated : rabbit-based antibody discovery platform that can generate and develop high quality, functional mAbs targeting traditional proteins and receptors as well as a wide variety of more challenging targets HuMab, our human antibody discovery engine acquired from MabVax Therapeutics in 2019, led to the clinical development of our fully human IgG1 monoclonal antibody product candidate targeting Sialyl Lewisa (sLea), a carbohydrate moiety that is present in over 90% of pancreatic and a large percentage of gastrointestinal cancers.

Answer 14

refer to slide 44

Answer 15

Developed for targets - Small molecule compounds are often developed for targets located within cells since they can enter the cells more easily due to their low molecular weight Combination therapies - They can also often be used synergistically in combination with other therapeutics such as mRNA, checkpoint inhibitors, radiation therapy and chemotherapy. Intrinsic benefits - Small molecules also often have other intrinsic benefits including relative ease and cost of production compared to larger compounds, as well as more frequently having the potential for oral administration to patients.

Answer 16

Immunomodulatory small molecule product class focuses on a range of endosomal and intracellular targets that are known to stimulate the activity of a wide range of immune cells. Particular emphasis on Toll-Like Receptors (TLRs). TLRs are a family of pattern recognition receptors that function as primary sensors of the innate immune system to recognize pathogens. TLRs represent a promising target class for cancer immunotherapy, particularly for inflammatory re-programming of the tumor microenvironment.

Answer 17

1. identify direct inhibitors Traditional drug discovery focuses on identifying direct inhibitors of target proteins. This typically relies on a measurable biochemical readout and accessible binding sites whose occupancy influences the function of the target protein 2. Undruggable Protein These requirements preclude many disease-causing proteins from being 'druggable' targets, and these proteins are categorized as 'undruggable’. 3. PROTAC The proteolysis-targeting chimera (PROTAC) technology provides powerful tools to degrade these undruggable targets and has become a promising approach for drug discovery

Answer 18

PROteolysis-TArgeting Chimeras (PROTACs) exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins. Recently, small-molecule PROTACs with high potency have been frequently reported. In this review, we summarize the emerging characteristics of small-molecule PROTACs, such as inducing a rapid, profound and sustained degradation, inducing a robust inhibition of downstream signals, displaying enhanced target selectivity, and overcoming resistance to small molecule inhibitors.

Answer 19

1. PROTACs regulate protein function by degrading target proteins instead of inhibiting them, providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions. 2. PROTACs have been proven to show better selectivity compared to classic inhibitors 3. PROTACs can be described as a chemical knockdown approach with rapidity and reversibility, which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations

Answer 20

refer to slide 56

Answer 21

refer to 57