Cancer cell–selective in vivo Treating cancer with light activated, antib onjugates by Amol Kapoor and Teddy Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren Rosenblum, Peter L Choyke & Hisataka Kobayashi near infrared photoimmunotherapy targeting specific membrane molecules
13
Embed
Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Cancer cell–selective in vivo
Treating cancer with light activated, antibody-dye conjugates
by Amol Kapoor and Teddy Leithead
Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren Rosenblum, Peter L Choyke & Hisataka Kobayashi
near infrared photoimmunotherapy targeting specific membrane molecules
Overview
• Cancer treatments focus on minimal side effects with maximal cancer cell death
• Photoimmunotherapy (PIT)
• IR700 + Trastuzumab and Panitumumab.
• IR700 toxic only when bound
• Specific antibodies could allow for the
treatment of many cancers
Background
Photo Dynamic Therapy (PDT)• Excited photosensitizers -> Singlet oxygen
• Singlet oxygen -> cell death
Immunotherapy
Uses the body's defense mechanism
Antibodies
Introduction
• PIT = PDT + Immunotherapy
• PDT -> Toxicity
• Immunotherapy -> Specificity
• PIT makes a strong therapy because of low healthy cell death
Review PDT PIT
Immunotherapy
Results-In Vitro
73% 78%
• 3T3-HER2 cells and A431 HER1 cells
• Significant cell death from both conjugates
• Irradiation -> Cell death
Results-In Vitro (Cont.)
• Tra-IR toxic only when bound
• Cellular uptake is unnecessary
Results-In Vivo
Results-In Vivo (Cont.)
• Tumor size
• Life span
Rats w/ treatment
•Repeated treatment of drug led to tumor free survival at over four months
Discussion
• IR700 is hydrophilic and has high extinction coefficient
•More effective than other photosensitizers.
• mAb-1700 is highly selective
•Conjugate is non-toxic when unbound
•Email from Kobayashi: Mechanism of action and FDA trials
Conclusion/Summary
• A target specific PIT was developed
•NIR light irradiation + the conjugate leads to large cancer cell death
•Highly effective in vitro and in vivo
Future Research
• For clinical trials, mAb-IR700’s toxicity mechanism must be understood
• Researchers must confirm a minimal threat to non-cancerous cells
• Unique mAbs -> PIT applied to multiple cancers for diagnosis and treatment
Why It Matters
• Completely Revolutionizes Field
•Potentially makes other drugs obsolete
•The likelihood of one of us getting cancer is high. Perfected, this offers a way to stop all cancers.