U01.02.040 Therapeutic antibodies: Autoimmune disease therapy

This guide provides an overview of key therapeutic antibodies, including their targets, clinical uses, and important notes for students preparing for the USMLE Step 1. Understanding these antibodies is critical for clinical applications, especially in oncology, autoimmune diseases, and other medical conditions.

1. Cancer Therapy

Agent	Target	Clinical Use	Notes
Alemtuzumab	CD52	Chronic lymphocytic leukemia (CLL), multiple sclerosis	“Alemtuzumab”—chronic lymphocytic leukemia
Bevacizumab	VEGF	Colorectal cancer, renal cell carcinoma, non-small cell lung cancer	Also used for neovascular age-related macular degeneration, proliferative diabetic retinopathy, and macular edema
Rituximab	CD20	B-cell non-Hodgkin lymphoma, CLL, rheumatoid arthritis, ITP, multiple sclerosis	Risk of progressive multifocal leukoencephalopathy (PML) in patients with JC virus
Trastuzumab	HER2	Breast cancer, gastric cancer	“Trastuzumab”—HER2-positive cancers, HER2-related therapies

2. Autoimmune Disease Therapy

Agent	Target	Clinical Use	Notes
Adalimumab, Infliximab	Soluble TNF-α	Inflammatory bowel disease (IBD), rheumatoid arthritis, ankylosing spondylitis, psoriasis	Etanercept is a decoy TNF-α receptor (not a monoclonal antibody)
Eculizumab	Complement protein C5	Paroxysmal nocturnal hemoglobinuria
Ixekizumab, Secukinumab	IL-17A	Psoriasis, psoriatic arthritis
Natalizumab	α4-integrin	Multiple sclerosis, Crohn disease	α4-integrin: WBC adhesion; Risk of PML in patients with JC virus
Ustekinumab	IL-12/IL-23	Psoriasis, psoriatic arthritis

3. Other Applications

Agent	Target	Clinical Use	Notes
Abciximab	Platelet glycoproteins IIb/IIIa	Antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention	“ABC is as easy as 123”
Denosumab	RANKL	Osteoporosis; inhibits osteoclast maturation (mimics osteoprotegerin)	“Denosumab helps make dense bones”
Omalizumab	IgE	Refractory allergic asthma; prevents IgE binding to FcεRI
Palivizumab	RSV F protein	RSV prophylaxis for high-risk infants	“PaliVIzumab—VIrus”

Key Points to Remember

Cancer Therapy: Antibodies like alemtuzumab, bevacizumab, and rituximab target specific antigens involved in tumor cell growth and angiogenesis.
Autoimmune Disease Therapy: Antibodies such as adalimumab, infliximab, and eculizumab are used to target TNF-α or complement proteins to reduce inflammation.
Other Applications: Abciximab and denosumab focus on platelet aggregation and osteoclast inhibition, respectively.

Important Notes for USMLE Preparation

Alemtuzumab and rituximab have notable risks like PML in JC virus-positive patients.
Bevacizumab is versatile in treating cancers and eye conditions.
Omalizumab works by blocking IgE in allergic asthma, crucial for understanding allergic responses.
Recognize the specific mechanisms of action for each antibody and its use in different conditions.

Understanding these agents’ mechanisms, clinical indications, and side effects will be important for answering USMLE Step 1 questions related to therapeutic antibodies.

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