Transcript Document
Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules 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 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 • 3T3-HER2 cells and A431 HER1 cells • Significant cell death from both conjugates • Irradiation -> Cell death 73% 78% 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 •Repeated treatment of drug led to tumor free survival at over four months Rats w/ treatment 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 noncancerous 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.