Totonchy Study Guide - work in progress

What does the suffix "-ximab" indicate about a monoclonal antibody?

It is chimeric

What does the suffix "-zumab" indicate about a monoclonal antibody?

It is humanized

What does the suffix "-omab" indicate about a monoclonal antibody?

It is mouse-derived

What does the suffix "-umab" indicate about a monoclonal antibody?

It is fully human

Rituximab is a monoclonal antibody. What type is it based on its name?

Chimeric

Trastuzumab is a monoclonal antibody. What type is it based on its name?

Humanized

Muromonab is a monoclonal antibody. What type is it based on its name?

Mouse-derived

Adalimumab is a monoclonal antibody. What type is it based on its name?

Fully human

Bevacizumab is a monoclonal antibody. What type is it based on its name?

Humanized

Cetuximab is a monoclonal antibody. What type is it based on its name?

Chimeric

Which applications of mAb therapeutics require the Fc region?

TNF alpha therapeutics

• Infliximab

• Adalimumab

• Etanercept

What is one stability advantage of nanobodies compared to mammalian immunoglobulins?

Nanobodies are more resistant to pH changes and denaturation

Nanobodies are easier to manufacture because they are composed of only ______

one protein

True or False: Nanobodies have a longer half-life than mammalian immunoglobulins

False. Nanobodies have a shorter half-life compared to mammalian immunoglobulins

What is one drawback of the small size of nanobodies as therapeutics?

Reduced bioavailability

True or False: Nanobodies do not require an identified target for their use.

False. Nanobodies require an identified target for therapeutic applications

The Fc region of a monoclonal antibody is required for applications such as ______ therapeutics

TNF alpha

What does an antibody with an Fc region look like?

See image

Name three monoclonal antibodies used as TNF alpha therapeutics.

Infliximab, Adalimumab, and Etanercept

Which applications require two antigen binding sites and what are these antibodies

called?

Cross linking

• Emicizumab

• Bispecific antibody

Which applications require a small structure like a fragment?

Single Chain mAb application

• Nanobody

What terms are used for therapeutics that use the patient’s own cells?

Autogenic/autologous

What terms are used for therapeutics that use other people’s cells?

Allogenic/heterologous

What is a major limiting factor for the development of CAR T cell therapeutics?

The need for a defined protein target

Why must CAR T cell targets be highly specific?

To avoid off-target toxicities

True or False: CAR T cell therapy can target any protein regardless of its specificity

False. CAR T cell therapy requires a specific target to minimize off-target toxicities

What is an example of "on-target but off-tumor" toxicity in CAR T cell therapy?

Targeting CD19 in tumor cells but also destroying normal B cells that express CD19, leading to immunosuppression

What systemic toxicity is commonly associated with CAR T cell therapy?

Cytokine storm caused by the activation and proliferation of CAR T cells

The systemic cytokine toxicities in CAR T cell therapy result from the activation of the ______

immune system

What is the goal of gene silencing in gene therapy?

To reduce or prevent the expression of a protein from a mutated gene

True or False: Gene silencing is a permanent solution to fix defective genes

False. Gene silencing is temporary and requires continuous therapy

What is the advantage of gene silencing in gene therapy?

It eliminates overactive defective genes without causing permanent alterations

What is the purpose of genome editing in gene therapy?

To fix the mutated gene directly

True or False: Genome editing in gene therapy has no risks of unintended effects.

False. Genome editing can cause off-target mutations

What is ectopic expression in gene therapy?

Adding a good copy of the mutated gene to restore function

Ectopic expression often uses ______, which can be dangerous

viral vectors

What is a disadvantage of ectopic expression in gene therapy?

It may not result in long-term effects for all applications

What are the three approaches for gene therapy?

• Gene silencing

• Genome editing

• Ectopic expression

Which type of virus used in gene therapy is mostly episomal but can also integrate?

Adeno-associated virus (AAV)

True or False: Adeno-associated virus (AAV) is always an integrating vector.

False. AAV is mostly episomal but can sometimes integrate

What type of vector is lentivirus in gene therapy?

Integrating vector

The ______ platform is an episomal vector used in gene therapy

HSV1 STAR-D

True or False: Lentivirus is an episomal vector.

False. Lentivirus is an integrating vector

What is the only FDA approved oncolytic therapeutic (only specific therapeutic

mentioned on the exam)

Imlygic

What are the ethical and practical reasons behind placebo choice for vaccine clinical trials.

Should mimic the same side effects but still not put the patient at risk. Patients

should still have equal protection from the disease.

Which vaccine types require specific target antigens to be selected during development?

• Subunit

• Recombinant

• mRNA

• Viral vector

• Conjugate