• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Ichor Intern Report: Dan Kalina

dan kalina kelsey moody ichor therapeutics

  • Please log in to reply
No replies to this topic
⌛⇒ MITOMOUSE has been fully funded!

#1 Mind

  • Life Member, Moderator, Secretary
  • 16,455 posts
  • 2,000
  • Location:Wausau, WI

Posted 21 September 2019 - 10:48 AM


Dan Kalina, Graduate Research Assistant, Biochemistry Graduate Student

My research at Ichor is focused on engineering an antibody-like protein scaffold into targeted and highly specific therapies. What does that mean, exactly? The next time you’re watching TV and a drug commercial pops up, take a look at the name of the drug – if it ends with ‘-mab’, it’s what’s known as a monoclonal antibody (mAb). Since the first mAb therapy, muromonab, gained FDA approval in 1986, over 500 different mAbs have been approved or are being investigated for a myriad of diseases. Antibody treatments have very specific mechanisms of action, usually making them highly efficacious drugs with minimal side effects. They are often described with a ‘lock and key’ model – antibodies will bind tightly to their specific target once it is presented, with minimal off-target effects. Their biggest downside is cost – complex, full-length protein structures are costly to produce and are highly unstable. Antibodies are inherently fragile and contain tightly woven molecular structures which must be kept intact for full functionality. Prolonged storage, freezing and thawing, and temperature changes or exposure to room temperature will quickly and irreversibly denature antibodies, rendering them useless. This, combined with the complexity of production, makes antibody therapies expensive options for patients in developed countries, and often inaccessible to third-world and developing areas[1][2]. In the US, for one year of treatment (excluding hospital fees), the average mAb is $96,731, and $142,833 for cancer mAb treatments, with many exceeding $200,000[2]. Currently at Ichor, I’m developing a cost-effective protein scaffold which may be a suitable replacement for some antibody therapies. It has been shown to have antibody-like specificity for engineered target sequences, is incredibly heat and pH stable (Tm ~ 102C, pH stable 4-10), can be made orally-bioavailable and survive the GI tract, is easily expressed in E. Coli, and can be produced for a fraction of the cost of mAbs[3]. Importantly, the exterior of our protein can be modified to recognize specific sequences without affecting its larger structure or stability – similar to mAbs. Our immediate goal is to prove efficacy against any therapeutically relevant targets, but we eventually hope to use RPtag’s uniquely stable properties in targeting novel anti-aging pathways which have been largely unreachable by mAbs, such as the GI tract.

We still have a long development road ahead of us, but we hope to one day be able to provide people with inexpensive and highly effective therapies for life-threatening diseases.

 

  1. Elmore, S. NIH Public Access. 35, 495–516 (2007).

  2. Hernandez, I. et al. THE AMERICAN JOURNAL OF MANAGED CARE ® Pricing of Monoclonal Antibody Therapies: Higher If Used for Cancer? 24, (2016).

  3. Derosa, J. R. et al. RPtag as an Orally Bioavailable, Hyperstable Epitope Tag and Generalizable Protein Binding Scaffold. Biochemistry 57, 3036–3049 (2018).

 

Attached Files







Also tagged with one or more of these keywords: dan kalina, kelsey moody, ichor therapeutics

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users