Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by...
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Transcript of Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by...
![Page 1: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/1.jpg)
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
![Page 2: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/2.jpg)
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
![Page 3: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/3.jpg)
Background
Photo Dynamic Therapy (PDT)• Excited photosensitizers -> Singlet oxygen
• Singlet oxygen -> cell death
Immunotherapy
Uses the body's defense mechanism
Antibodies
![Page 4: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/4.jpg)
Introduction
• PIT = PDT + Immunotherapy
• PDT -> Toxicity
• Immunotherapy -> Specificity
• PIT makes a strong therapy because of low healthy cell death
![Page 5: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/5.jpg)
Review PDT PIT
Immunotherapy
![Page 6: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/6.jpg)
Results-In Vitro
73% 78%
• 3T3-HER2 cells and A431 HER1 cells
• Significant cell death from both conjugates
• Irradiation -> Cell death
![Page 7: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/7.jpg)
Results-In Vitro (Cont.)
• Tra-IR toxic only when bound
• Cellular uptake is unnecessary
![Page 8: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/8.jpg)
Results-In Vivo
![Page 9: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/9.jpg)
Results-In Vivo (Cont.)
• Tumor size
• Life span
Rats w/ treatment
•Repeated treatment of drug led to tumor free survival at over four months
![Page 10: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/10.jpg)
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
![Page 11: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/11.jpg)
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
![Page 12: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/12.jpg)
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
![Page 13: Cancer cell–selective in vivo Treating cancer with light activated, antibody-dye conjugates by Amol Kapoor and Teddy Leithead Makoto Mitsunaga, Mikako.](https://reader036.fdocuments.net/reader036/viewer/2022081519/56649ec65503460f94bd20ca/html5/thumbnails/13.jpg)
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.