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.