This is a patented technology that disrupts cancer’s immunological homeostasis and drives cancer cells into normalcy (apoptosis) through manipulation of the cancer-induced homeostasis. (patent #9.919.000)
Michael Lytinas is an independent inventor based in Boston, Massachusetts. Following his PhD in inflammation from Tufts Medical School, his research focuses on cancer from the inflammation angle, and more specifically from the immunological imbalance that cancer creates.
Normal cell vs Cancer cell Physiology
For a healthy cell, the environment is slightly acidic inside the cell and slightly alkaline outside.
Cancer cells have the opposite pH gradient of normal cells: they are alkaline inside-acidic outside.
Characteristics of the cancer cell membrane vs healthy cell:
-Multiple proton pumps for pH homeostasis
-Multiple glucose receptors to increase access to fuel
To maintain this reverse pH gradient they develop multiple proton pumps to expel the increased number of protons produced in the cytosol. Cancer cells expel protons to survive, proliferate and metastasize. The rate of proton expulsion from the cell is a direct indicator of the degree of the malignancy. Peritumoral acidity is a factor in the resistance to chemotherapy and radiotherapy. Cancer cells have increased metabolic needs and for this reason they develop many receptors for glucose or other metabolic fuel in their membranes.
What we are trying to do is to manage protons, either inside or outside of the cancer cell
This technology is trying to create new molecules that deal with the excessive amount of the newly formed protons, either inside or outside of the cancer cell. The inside the cell way is to deliver protons back into the cytosol of the cancer cells, acidifying the cancer cytosol de novo and triggering apoptosis. The outside of the cell way is to neutralize the protons in the extracellular space, triggering an immunological response. It can also help to alleviate the pain in metastatic breast cancer patients that is often associated with the acidic cancer microenvironment.
Cancer cells have an increased affinity for certain fuel molecules. This technology uses a cancer preferred metabolic fuel -glucose or glutamine or fatty acids, etc.- to navigate to the cancerous site. In the inside the cell way, this technology delivers protons inside the cancer cell. The trigger for the release of these protons is the slightly alkaline intracellular environment. In the outside the cell way, this technology reaches the cancer cells and neutralizes the extracellular protons. The trigger for this neutralization is the acidic nature of the extracellular cancer microenvironment.
How does this technology work
Inside the cell
In order to facilitate an easier entrance into the cancer cell, this technology utilizes a preferred cancer fuel that carries its own protons. The molecule enters the cancer cell and delivers the protons inside the cytosol. The slightly alkaline environment of the intracellular space is the trigger that releases the protons inside the cell. The acidification of the cancer cytosol drives the cell’s own apoptotic mechanisms.
Outside of the cell
Following cancer cells’ increased metabolic activity, this technology uses a cancer preferred fuel to navigate to the tumor side, bringing a proton scavenger. The acidic cancer microenvironment opens up the proton scavenger and neutralizes the protons that are abundant in the extracellular space. The reduction of the acidity of cancer microenvironment triggers immunological responses, e.g., cytokine release or monocyte migration.
Therefore this approach works by disrupting cancer’s own pH homeostasis.
In vivo data
Histology slides showing the effect of a compound based on this technology in a 4T1 mouse metastatic breast cancer model (hBrCa analogue).
Control (far left) vs treated (middle and right slide), showing 48% tumor reduction after 4 days of IV injections.
No body weight change was observed in the treated mice.
Therapeutic opportunities with minimal side effects
Metastatic breast cancer patients may benefit from this technology:
by triggering therapeutic immunological responses inside or outside the cancer cell
and by lowering the pain which is often associated with the cancer acidic microenvironment
The main focus of this technology is to trigger immunological responses in the cancer environment without disrupting the metabolic activity in healthy tissue. This way, the potential of side effects is reduced.
At a glance
Cancer is mimicking the metabolic profile of a healing wound. To achieve that, cancer reverses the pH gradient. If we reverse this sequence of events and turn the pH gradient back to normal again, the cancer will succumb to its own apoptotic mechanisms.
In order to do that, the inventor is looking for:
collaboration with scientists for the creation of chemical compounds based on this approach
funding for the development of this project
Michael Lytinas DDS, PhD