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Cancer cell–selective in vivo

near infrared photoimmunotherapy targeting specific membrane molecules. Cancer cell–selective in vivo. Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren Rosenblum, Peter L Choyke & Hisataka Kobayashi.         Treating cancer with light activated, antibody-dye conjugates

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Cancer cell–selective in vivo

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  1. near infrared photoimmunotherapy targeting specific membrane molecules Cancer cell–selective in vivo Makoto Mitsunaga, Mikako Ogawa, Nobuyuki Kosaka, Lauren Rosenblum, Peter L Choyke & Hisataka Kobayashi         Treating cancer with light activated, antibody-dye conjugates               by Amol Kapoor and Teddy Leithead

  2. 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

  3.    Background Photo Dynamic Therapy (PDT) • Excited photosensitizers -> Singlet oxygen • Singlet oxygen -> cell death •     Immunotherapy • Uses the body's defense mechanism • Antibodies

  4. Introduction • PIT = PDT + Immunotherapy • PDT -> Toxicity  • Immunotherapy -> Specificity  • PIT makes a strong therapy because of low healthy cell death

  5. Review PDT                                                                      PIT                             Immunotherapy

  6. Results-In Vitro • 3T3-HER2 cells and A431 HER1 cells • Significant cell death from both conjugates • Irradiation -> Cell death 73% 78%

  7. Results-In Vitro (Cont.) • Tra-IR toxic only when bound • Cellular uptake is unnecessary

  8. Results-In Vivo

  9. Results-In Vivo (Cont.) • Tumor size • Life span • Repeated treatment of drug led to tumor free survival at over four months Rats w/ treatment

  10. 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

  11. 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

  12. 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

  13. 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.

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