137 and Photodynamic Therapy and Photoimmunotherapy

1 month 2 weeks ago - 1 month 2 weeks ago #60997 by joea73
Number 137

When you surf often on the internet, you may encounter something you have never heard of, but it can be a very intriguing story.   Number 137 is such an intriguing story I have encountered recently. If you are a physicist , you may be familiar with 137. Arthur Miller, an emeritus professor of history and philosophy of science at University College London says "137 continues to fire the imagination of everyone from scientists and mystics to occultists and people from the far-flung edges of society,".  To physicists, 137 is the approximate denominator of the fine-structure constant (1/137.03599913), the measure of the strength of the electromagnetic force that controls how charged elementary particles such as the electron and nuon interact with photons of light, according to the National Institute of Standard and Technology.  The fine-structure constant is one of the key physical constants of the universe. "This immutable number determines how stars burn, how chemistry happens and even whether atoms exist at all,"  Michael Brooks, a science writer says.   I don’t understand most of what it says but it sounds like 137 is a special number for physicists.   The formula of finite structure constant is shown below.   

alpha= ke2 hc =1/137    

alpha= Finite structure constant
k   =  Coulomb’s constant
e   =  elementary charge
h   = reduced Planck constant
c   = speed of light in vacuum

Photodynamic therapy

The reason I decided to chit chat  about 137 is to tell how I encountered the number 137 myself recently.  I was reading up on the subject of Photodynamic Therapy and Photo-Immunotherapy for bladder cancer.  Photodynamic therapy as cancer treatment is to utilize radical oxygen species which are produced by exciting photosynthesizer by exposing it to light.   Plants take water(H2O) and carbon-dioxide(CO2) and sunlight to make their own food - Glucose/Sugar (C6H12O6). As by-product, it produces oxygen (O2) which we breathe in.  This process is called photosynthesis.  This photosynthesis also produces reactive oxygen species - oxygen molecules which lack an electron. Those reactive oxygen species are harmful because they steal an electron from another molecule so the reactive oxygen becomes stable. The reactive oxygen steals an electron from a chemical molecule of a cell including a cancer cell, this makes a part of the cell not functional, in another term, it can injure the cell by damaging the outer membrane, protein, and DNA leading the cell to death.  Photodynamic therapies try to kill cancer cells by producing radical oxygen species by photosynthesis using its unique photosynthesizer and a special lighting device.  The photosynthesizer in plants is chlorophyll.
Its molecular structure is shown in the link at the bottom.   As you can see, there is a magnesium atom in the center.  My first encounter with the mystery of life is to realize that the molecular structure of chlorophyll is almost identical to the molecular structure of hemoglobin (red blood cell) in our body. The main difference is the center of molecular structure of hemoglobin is ion (Fe) where the center of molecular structure of chlorophyll in plants is magnesium (Mg).  Do I and plants share the same past??

The 2nd encounter or the encounter to the number 137 is that the chemical formula of chlorophyll is C55H72MgN4O5.  It is made up of 55 carbon atoms, 33 hydrogen atoms, 1 magnesium atom, 4 nitrogen atoms, and 5 oxygen atoms.  When you add up the number of atoms in chlorophyll -> 55 + 72 + 1 + 4 +5 = 137.  You may say it is just a coincidence.  

There have been several photosynthesizers developed mimicking the structure of chlorophyll
 and used to treat cancer. Some  photosynthesizers to treat cancers are given intravenously and others are applied topically.  The photosynthesizer has to reach certain depth to reach all cancer cells and the light source must reach enough depth to excite all photosynthesizer molecules.

Though PDT has been applied to cancers such as esophageal cancer, its application to bladder cancers have been small scale tests and studies.   In recent years, a Canadian laser treatment company developed PDT for BCG unresponsive bladder cancer.  Their photosynthesizer chemical uses Ruthenium, a rare metal which belongs to the platinum group in the chemical table.  Phase 1 had been completed a while ago and now they are in Phase 2. 

Photoimmunotherapy

Meanwhile, photo-immunotherapy had been developed by a scientist in National Cancer Institute and it had been approved in Japan to treat certain cancers.. It is also in Phase 3 in FDA clinical trials.  It is not like generally understood check point inhibitors immunotherapy such as Pembrolizumab (keytruda by Merck), Avelumab (Bavencio by Pfizer), Atezolizumab (Tecentriq by Roche), etc.. It is photodynamic therapy in the context that it has its own photosynthesizer called IR7000. It uses near infrared light to excite the synthesizer.  So, I find that the term immunotherapy has some marketing spin and may confuse the patients.  Nevertheless its mechanism of action to kill cancer cells and how to selectively damage cancer cells but not normal cell is very different from conventional PDT.  It is an antibody conjugate with the photosynthesizer as payload.  PSS - IR7000 in administered intravenously,  The patient
waits a day or two till the antibodies bind to a target protein on the cancer cells. Then near infrared light is exposed to the location of the cancer,  The light excites the photosynthesizer - IR7000.  Instead of generating harmful radical oxygen species, the light hardens IR7000. 
This phenomenon of hardening near the cancer cells makes holes in the outer cell membrane, which triggers water (H2O) in our body to flow into the cancer cells, causing the cancer cells to expand and explode and die.  Other cancer treatments such as chemotherapy, radiation therapy,immunotherapy and even conventional PDTs utilize chemical reactions to damage
cancer cells but this photo-immunotherapy physically damages cancer cells. So it is an instant kill.  A recent article on this Near-infrared photoimmunotherapy (NIR-PIT) 

“Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy that directly kills cancer cells as well as producing a therapeutic host immune response. Conventional immunotherapies, such as immune-activating cytokine therapy, checkpoint inhibition, engineered T cells and suppressor cell depletion, do not directly destroy cancer cells, but rely exclusively on activating the immune system. NIR-PIT selectively destroys cancer cells, leading to immunogenic cell death that initiates local immune reactions to released cancer antigens from dying cancer cells. These are characterized by rapid maturation of dendritic cells and priming of multi-clonal cancer-specific cytotoxic T cells that kill cells that escaped the initial direct effects of NIR-PIT”   

Anyway, the group started with head and neck cancer treatment with photoimmunotherapy and it is in phase 3 clinical trial. Japan minister of health already approved NIR-PIT to treat head and neck cancer.  

The inventor of NIR-PIT says it can deal with about 80% of cancers. In terms of bladder cancer,
The study was published already in 2018. In the study, they tested on mice and by creating antibody targeting a caine anti-epidermal growth factor receptor (EGFR) protein, which is often over expressed in lung,colong, head and neck, and bladder cancer.   The study focused on muscle invasive bladder cancer.  It worked well on mice. The study says NIR-PIT with can225-IR700 led to rapid cell death in vitro and tumor growth reduction and survival improvement in vivo.  

Stanford university team published their study for treatment of non invasive bladder cancer using NIR-PIT with CD47 (an innate immune check point which is widely expressed on bladder cancer cells antibody) as target for monocolonal antibody (mAb) - photo-absorber conjugate (APC).  “In summary, we show light dose dependent cytotoxicity of human bladder cancer cells with NIR-PIT using anti-CD47-IR700 as well as excellent in vivo tumor control. With additional clinical studies, we envision that anti-CD47-IR700 NIR-PIT could serve as adjuvant therapy after TURBT followed by weekly NIR-PIT treatment in an office-based setting to improve management of bladder cancer.”.

Lets hope that NIR-PIT becomes another viable treatment for bladder cancers.

My daughter says mine writing is  always TLDR (too long do not read).  Well that is why I post it in Chit Chat section.

best

References 

Chemical structure of chlorophyll of plant and hemoglobin of human

patch.com/georgia/cascade/bp--hemoglobin-vs-chlorophyll

photoimmunotherapy related

clinicaltrials.gov/ct2/show/NCT02422979
 academic.oup.com/intimm/article/33/1/7/5851356
www.ncbi.nlm.nih.gov/pmc/articles/PMC5922375/
pubmed.ncbi.nlm.nih.gov/30890547/
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