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New gen therapeutics letsgooo Flashcards

1
Q

what is newgen therapeutics

A

NewGen Therapeutics is focused on the discovery and development of targeted small molecule drugs to treat cancer patients.

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2
Q

what is immunotherapy

A

Cancer immunotherapy harnesses the patient’s own immune system to fight against cancer, which directly target the tumor cells.

Immunotherapy has been an effective treatment for patients with certain types of cancer that have been resistant to chemotherapy and radiation treatment (e.g., melanoma).

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3
Q

How does the immune system work? Lymph nodes

A

Small glands located throughout the body that filter bacteria , viruses – even cancer cells – which are then destroyed by special white blood cells. Also the site where T cells are “educated” to destroy harmful invaders in your body

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4
Q

How does the immune system work? Bone marrow

A

Soft, sponge-like material found inside bones. Contains immature cells that divide to form more blood-forming stem cells , or mature into red blood cells, white blood cells (B cells and T cells), and platelets

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5
Q

How does the immune system work? Spleen

A

Organ located to the left of the stomach. Filters blood and provides storage for platelets and white blood cells. Also serves as a site where key immune cells (B cells) multiply in order to fight harmful invaders

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6
Q

How does the immune system work? Appendis

A

Thin tube about 4 to 6 inches long in the lower right abdomen. The exact function is unknown, one theory is that it acts as a storage site for “good” digestive bacteria

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7
Q

How does the immune system work? Thymus Gland

A

Small gland situated in the upper chest beneath the breastbone. Functions as the site where key immune cells (T cells) mature into cells that can fight infection and cancer

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8
Q

6 types of cancer immunotherapy: Immune checkpoint inhibitors

A

which are drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer.

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9
Q

6 types of cancer immunotherapy: Tumor Antigen Targeting Antibodies

A

are laboratory generated, designed to target specific tumor antigens, usually conjugated with a specific drug. Currently the development of polyspecific antibodies (bi- and tri-specific antibodies) has the advantages by targeting multiple tumor antigens, to more precisely and effectively eradicate cancer cells

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10
Q

6 types of cancer immunotherapy: recombinant cytokines

A

can induce, mediate and regulate the immune response by improving antigen priming, facilitating T cell proliferation and survival or enhancing their cytolytic activity.(e.g., IL-2, IL-18, IL-6, IFNγ, GM-CSF)

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11
Q

6 types of cancer immunotherapy: therapeutic vaccines

A

made of laboratory modified cancer cells, parts of cells, or pure antigens elicit an immune response against tumor-specific or tumor-associated antigens

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12
Q

6 types of cancer immunotherapy: oncolytic viruses

A

in the forms of native or engineered viruses can be used to selectively target and kill cancer cells. Advancements of genetic engineering enable successful editing of viral genome of many species to augment antitumor activity and attenuate pathogenicity, but also to express

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13
Q

6 types of cancer immunotherapy: CAR T Cell and adoptive cell therapy ACT

A

are personalized cancer strategies relying on the collection of immune cellular components from patient, expansion and/or genetically modification of those cellsin vitroand injection them back to the patient to achieve a therapeutic response.

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14
Q

Biontech SE making individualized cancer therapies a reality

A

BioNTech developer of vaccines, immunomodulators, and cell therapies for treating multiple cancers.
The company’s proprietary platform is used to develop mRNA-based drugs, Chimeric Antigen Receptors-based products and antibody checkpoint immunomodulators.
Its drug pipeline includes several vaccines for different cancers such as melanoma, head/neck cancer, and breast cancer.
It also develops T cell therapies, engineered nanoparticles for cancer immunotherapy, small molecule drugs and biomarker-based in vitro diagnostic devices.

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15
Q

structural elements of mRNA

A

potential immunogenicity
efficacy of translation
stability of molecule

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16
Q

4 characteristics of mRNA therapeutics

A

Natural molecule found universally within cells, with well-characterized properties.

Transient, with adaptable activity and half-life. Avoids genomic integration problems sometimes seen in gene therapy, potentially resulting in a better safety profile.

Suitable to encode for antibodies, antigens, cytokines and any other type of protein.

Can be designed and optimized pharmacologically and immunologically, making it suitable for a broad range of applications.

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17
Q

the 4 different types of mRNA format

A

Optimised unmodified mRNA
(uRNA)

Nucleoside-modified mRNA (modRNA)

Self-Amplifying mRNA
(saRNA

Trans-Amplifying mRNA
(taRNA

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18
Q

Optimised unmodified mRNA

uRNA

A

Repeat administrationStrong T cell responses

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19
Q

Nucleoside-modified mRNA (modRNA)

A

Non-immunogenic vectorStrong antibody responsesTherapeutic protein delivery

20
Q

Self-Amplifying mRNA

(saRNA

A

Sustained expressionT cell responses upon prime onlyProtection upon prime only

21
Q

Trans-Amplifying mRNA

(taRNA

A

Sustained expressionHighly flexible co-transferLow antigen RNA doses

22
Q

Process of Optimised unmodified mRNA

uRNA

A

Vaccines based on sequence optimized, chemically unmodified mRNA formulated in optimized lipid nanoparticles (LNPs) are highly immunogenic and well tolerated in non-human primates (NHPs).

First mechanistic insights into the mode of action of the LNP-formulated mRNA vaccines demonstrated a strong activation of the innate immune response at the injection site and in the draining lymph nodes (dLNs).

Activation of the innate immune system was reflected by a transient induction of pro-inflammatory cytokines and chemokines and activation of the majority of immune cells in the dLNs.

Immunogenicity of the mRNA is an added benefit when mRNA is used for immunotherapy applications, by acting as an immunotherapy adjuvant.

23
Q

Nucleoside-modified mRNA (modRNA)

A

modRNA is a syntheticmessenger RNA(mRNA) in which somenucleosidesare replaced by other naturallymodified nucleosidesor by syntheticnucleosideanalogues. modRNA is used to induce the production of a desired protein in certain cells.

The presence of a variety of modified nucleosides in the manufactured mRNA lead to superior protein production for long duration.

Deimmunizing mRNA by incorporating modified nucleosides helps to avoid production of anti-drug antibodies and broadens the therapeutic application of these types of mRNA drugs.

24
Q

Self-Amplifying mRNA

saRNA

A

saRNA drugs use the concept of viral replication, while not being an infectious, disease-causing agent itself

Efficient delivery ofnucleic acidto the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein.

Resembles conventional mRNA encoding the protein of interest, but also encoding a polymerase, called replicase, that multiplies part of the mRNA within the target cell.

During self-amplification inside the cell, a double-stranded RNA intermediate is generated, which is recognized by intracellular immune sensors.

This makes saRNA a very potent activator of the immune system and therefore an excellent category of immunotherapy.

25
Q

Trans-Amplifying mRNA

taRNA

A

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.

26
Q

comparison table between attentuated/inactivated vaccine, subunit vaccine, DNA vaccine, mRNA

A

refer to notes

27
Q

engineered cell therapies

A

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.

28
Q

antibodies therapy

A

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

29
Q

how does antibody therapy work

A

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.

30
Q

monoclonal antibodies

A

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.

31
Q

how does monoclonal antibodies work

A

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

32
Q

immunogenicity

A

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

33
Q

use of monoclonal antibodies

A

Low immunogenicity
High antigen binding activity
high stability

34
Q

3 ways monoclonal antibodies drugs work

Block

A

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.

35
Q

3 ways monoclonal antibodies drugs work

Flag

A

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

36
Q

3 ways monoclonal antibodies drugs work

Deliver

A

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.

37
Q

BionTech mAb

A
  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.

38
Q

The workflow of antibody humanization and optimization and how the computer-aided antibody design contributes

A

refer to slide 44

39
Q

small molecule immunomodulator

A

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.

40
Q

Toll like receptors

A

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.

41
Q

Degrader technologies

A
  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
42
Q

PROTAC

A

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.

43
Q

PROTAC 3 characteristics

A
  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
44
Q

comparisons of PROTAC with other therapeutic modalities

A

refer to slide 56

45
Q

How Protac use our cells’s natural disposal system to kill cancer causing proteins?

A

refer to 57

TRCML (6 decks)

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