Theralase Technologies Inc. V.TLT

RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:PP speculation

[CancerSlayer]

Eoganacht wrote: Thanks for the post DJDawg. It all sounds right to me.

They have demonstrated that Rutherrin works much better than TLD1433 by itself as an anti-cancer PS. When I wrote them years ago to ask why they were using TLD1433 (Ruvidar) rather than Rutherrin in the NMIBC trial they told me that Rutherrin just wasn't ready yet. Theralase was in no position to wait another year or two before starting the phase 1 trial.

This from Pavel Kaspler and colleagues 2016 pqper:

We present data showing that premixing the Ru2+-complex TLD1433 with transferrin increases the molar extinction coefficient, including longer activation wavelengths, reduces photobleaching rates, reduces the toxicity of the complex and improving overall PDT efficacy. As the transferrin receptor is upregulated in most malignancies, premixing of the Ru2+ complex with transferrin converts the active pharmaceutical ingredient TLD1433 into a drug of potentially considerable clinical utility. 

Ruthenium(II) based Photosensitizer and Transferrin Complexes Enhance Photo-physical Properties, Cell Uptake, and Photodynamic Therapy Safety and Efficacy

This all begs the question - once the current NMIBC trial is complete and Theralase is adequately funded at last, wouldn't it make sense to conduct a new NMIBC trial using Rutherrin rather than Ruvidar? Maybe they would get even better results.

DJDawg wrote:
A few add on comments (please correct me if anything I say is incorrect)

Ruvidar is the brand name for tld-1433, for the bladder

My understanding is that Rutherrin is the brand name for tld-1433 combined with transferrin.
Transferrin is a protein that floats around in blood and binds iron. It then presents itself to the outside of a cell. If the cell needs iron it expresses way more of something called transferrin receptor. Cancer cells have been show to have a lot of transferrin receptors as they are trying to grab any iron passing by. TLD-1433, contains ruthenium which is in the same column of the period table as iron. Same column means many similar properties. So transferrin protein seems to happily bind to tld-1433 and then when passing by, the cancer cell would grab it, assuming it is iron. Now it is in the cell. Trojan horsing it I guess.

I believe that the planned way to do this treatment is to premix the transferrin protein with the tld-1433 and then give it. That way already packaged and ready to go rather than depending on the tld-1433 wandering around looking for the patient's transferrin to bind to.

Eog can correct me but my understanding is Rutherrin is tld-1433 packaged together with transferrin to make the treatment drug.

Ran out of sparklers....Thanks for your informative posts Eog & DJDawg.

For those who may not already know....The true potential of TLD 1433/Ruvidar is certainly waiting to be unleashed in the form of Rutherrin.  From my understanding, TLD 1433 as a sole actor can only passively diffuse into a cancer cell, & the amount absorbed can be limited by various factors such as local drug concentration, cell membrane composition &/or membrane potential, etc.  Fortunately, TLD 1433 likes to hitch a ride with transferrin, enabling its smoother/less limited entry into a growing cancer cell.  

Any method that can effectively/efficiently deliver more drug to a cancer w/o harming its host should gain considerable favor in cancer treatment...too many current SOC treatments are limited by cost, insurers, drug toxicity, ineffectiveness, treatment-intensive protocols, patient burden/compromises, etc, etc.  It's going to be a fun ride for me to see how much Rutherrin can enhance TLD 1433 efficacy, not only possibly for NMIBC, but for the many other potential indications...either as a solo actor or partner...the latter taking further advantage via the many potential synergistic benefits.