ShimodaAtlantic™
Our Research
Research Programs
ShimodaAtlantic™
specializes in niche
pharmaceutical programs with emphasis in
adult and pediatric oncology investigational
drug research.
Our current focus is on three distinct areas:
- nanotherapeutic drugs designed to destroy cancer tumors via apoptosis;
- exploration of
potential cancer vaccines based on heat shock proteins and cytokeratin fragments and subunits; and,
- phytotherapeutic agents manufactured for other labeled purposes, but for which promise apears possible as cancer drugs.
ShimodaAtlantic™
specializes in niche
pharmaceutical programs with emphasis in
adult and pediatric oncology investigational
drug research.
Our current focus is on three distinct areas:
- nanotherapeutic drugs designed to destroy cancer tumors via apoptosis;
- exploration of
potential cancer vaccines based on heat shock proteins and cytokeratin fragments and subunits; and,
- phytotherapeutic agents manufactured for other labeled purposes, but for which promise apears possible as cancer drugs.
Magnetite Particle Nanotherapy
Our nanotherapy investigation has its origins in research surrounding our investigational drug Xenavex™. In our current generation of investigational nanoparticle research, we are attempting to devise a mechanism of targeted delivery of a nanoparticle that is non-toxic to the patient, and enters only cancer cells. In in vitro studies, we have observed that this is destructive to neoplastic cells when externally triggered with a brief pulse of a small amount of low-frequency (118 kHz) alternating magnetic field (AMF) energy.
This project's objective is to destroy cancer cells through a process called "apoptosis." This process works when a cancer cell (but not a normal cell) ingests a treated magnetite or gold nanoparticle which is later heated by the AMF. Cancer cells normally die when heated beyond 109 degrees F. In practical terms, the approach is to kill cancer cells while sparing adjacent normal cells. An advantage to killing the cells in serial treatment cycles rather than ablating the cell on the first pass may be a phenomena discovered and reported by researchers at Nagoya University in Japan. In the Nagoya model, researchers killed tumors they induced in test animals by treating them in three cycles.
There appears to be a relationship between induced immunity in the Nagoya animals and their time vs. temperature model.
In their experience, test animals were able to mount an innate immune response to tumors that had not been treated with hyperthermia. The result was that large untreated tumor masses were subsequently destroyed by the animal's own immune system as a result of CD4+, CD8+ and targeted T-cell activity. Attempts to later reinfect and regrow these same animals with the original cancer cell line repeatedly failed on rechallenge, and the animals were observed mounting an immune response to the cancer cell line.
Other groups pursuing nanotherapies are dealing with particles in the 1 to 10 nanometer size range. While those companies are using monoclonal antibodies to attach their particles to cancer cells, we endeavor to attach a commercial lipid carrier to the nanoparticles of magnetite, and then label that package with glucose.The package then enters the neoplasm of a cancer cell through pinocytosis. By administering the nanoparticles through an intratumoral injection, we believe we can achieve a low-toxicity therapy protocol that will have the greatest likelihood of duplicating the Nagoya small-animal model in a human patient. Our novel approach of phased arrays of intersecting magnetic fields, enhanced with flux concentrators alows us to achieve hysteresis of the drug particles with relatively low energy, well under established and FCC approved threshholds for human exposure.
Our investigational drug is actually a nanostructure approximately 50-nanometers in size. It is designed to resonate and heat-up when excited with an external alternating magnetic field in the 50 ~ 120 kHz frequency spectrum. In in vitro studies, we have experimented with short duration AMF at power levels of less than 250 watts/cm2 with suitable particle response. Our present permits treatment of a targeted tumor at a distance of up to 20 cm from the energy source, thereby allowing treatment of deep-seated thoracic tumors in humans with minimal drug involvement.
Using a larger coated delivery vehicle labeled with glucose and other moities, we are able to take advantage of a phenomena associated with the vasculature in tumor structure capillaries - large fenestrations. These fenestrations, or "holes" result in openings some 20-times larger than a health capiillary. While a normal capillary opening is about 5nm, a tumor's capillaries have large openings, usually about 100nm.
Our delivery package cannot easily pass into normal cells through ordinary fenestrations. It does pass easily, however, into a tumor capillary structure. The glucose labeling encourages a cancer cell to take the package inside the cell structure.
We are partnering with the Veterinary Oncology Group at Situs Oncology by providing the equipment and test drug for its current clinical study of magnetic hyperthermia in cats and dogs. Small animals are being treated with curative intent. The induced immunity effect observed in murine models in the Nagoya studies is under investigation to see if there is a similar response in canine and feline models.
Xenavex™
Our Xenavex™ Phase II FDA clinical trial program will initially explore the effectiveness of a nerium oleander L. derivative, oleandrin, as a potential monotherapy for mesothelioma and non-small cell lung cancer. In the near term, additional Phase II studies are planned for the purpose of exploring efficacy of Xenavex™ in treating cancer of the breast, the prostate, BRO melanoma and pediatric medulloblastoma.
Xenavex™ (NDC14213-001/01/02/03) is an ethanolic botanical extract compound of various cardioglycosides derived from oleander, a toxic plant that has been investigated and used as a "traditional medicine" for over 1,000 years. Modern oleander based drugs have previously been made in both China and Russia, where they are used as cardiology drugs. Our experience thus far is that the ethanolic extraction process results in higher ratios of the active moieties than extractions made from other processes.
Pediatric cancers, such as primitive neuroectodermal tumor (PNET) (medulloblastomas) are very difficult to treat. Even successful cases result in devastating side effects to the patient. Xenavex™ crosses the blood/brain barrier, thereby suggesting its possible use in treating pediatric brain cancers. We anticipate participating in a separate Phase II program to investigate the potential of Xenavex™ labeled with a glucose-like substance as a pediatric cancer monotherapy. The program goal is to enhance movement of Xenavex™ across the blood-brain barrier on glucose transporter (GLUT) 3 in much larger ratios than its unaugmented entry on GLUT 1 and 2.
Xenavex™ is a prescription item for its labeled indications related to cardiovascular disease. It is not approved for any other indication such as a proliferative cell disorder. In October, 2004, after extensive consideration, ShimodaAtlantic changed its pollicy regarding availability of Xenavex™ to patients seeking access to the drug under single patient investigational new drug applications (FDA Form 1571). Since then, we have provided access to the drug to qualified physicians for either investigational or "off-label" usage. It is the policy of the company to discourage off-label use of the drug and to pursue access via the FDA's single patient IND program.
In late February 2005, we obtained a NDC (National Drug Code) numerical assignment for Xenavex™ in 3ml, 10ml and 30ml packages.
Autologous Vaccine & Immune Response Stimulation
Our early-stage vaccine project is investigating whether the human immune system can be stimulated to react to, and, destroy tumor cells, based on their unique protein structure.
European investigators have reported some success in triggering the body's natural immune response to cancer cells, by introducing protein fragments similar to those created by cancer cells, but in much larger quantities than a tumor normally produces.
Our current research focuses on heat shock protein (HSP) 70, cytokeratin-19 fragments and its CYFRA-21 subunits as being potential immune system stimulators.
The investigation will seek to determine if by introducing a large amount of the protein fragments, the immune response is enhanced, thereby triggering the body’s natural defense against cell disorders.
Our nanotherapy investigation has its origins in research surrounding our investigational drug Xenavex™. In our current generation of investigational nanoparticle research, we are attempting to devise a mechanism of targeted delivery of a nanoparticle that is non-toxic to the patient, and enters only cancer cells. In in vitro studies, we have observed that this is destructive to neoplastic cells when externally triggered with a brief pulse of a small amount of low-frequency (118 kHz) alternating magnetic field (AMF) energy.
This project's objective is to destroy cancer cells through a process called "apoptosis." This process works when a cancer cell (but not a normal cell) ingests a treated magnetite or gold nanoparticle which is later heated by the AMF. Cancer cells normally die when heated beyond 109 degrees F. In practical terms, the approach is to kill cancer cells while sparing adjacent normal cells. An advantage to killing the cells in serial treatment cycles rather than ablating the cell on the first pass may be a phenomena discovered and reported by researchers at Nagoya University in Japan. In the Nagoya model, researchers killed tumors they induced in test animals by treating them in three cycles.
There appears to be a relationship between induced immunity in the Nagoya animals and their time vs. temperature model.
In their experience, test animals were able to mount an innate immune response to tumors that had not been treated with hyperthermia. The result was that large untreated tumor masses were subsequently destroyed by the animal's own immune system as a result of CD4+, CD8+ and targeted T-cell activity. Attempts to later reinfect and regrow these same animals with the original cancer cell line repeatedly failed on rechallenge, and the animals were observed mounting an immune response to the cancer cell line.
Other groups pursuing nanotherapies are dealing with particles in the 1 to 10 nanometer size range. While those companies are using monoclonal antibodies to attach their particles to cancer cells, we endeavor to attach a commercial lipid carrier to the nanoparticles of magnetite, and then label that package with glucose.The package then enters the neoplasm of a cancer cell through pinocytosis. By administering the nanoparticles through an intratumoral injection, we believe we can achieve a low-toxicity therapy protocol that will have the greatest likelihood of duplicating the Nagoya small-animal model in a human patient. Our novel approach of phased arrays of intersecting magnetic fields, enhanced with flux concentrators alows us to achieve hysteresis of the drug particles with relatively low energy, well under established and FCC approved threshholds for human exposure.
Our investigational drug is actually a nanostructure approximately 50-nanometers in size. It is designed to resonate and heat-up when excited with an external alternating magnetic field in the 50 ~ 120 kHz frequency spectrum. In in vitro studies, we have experimented with short duration AMF at power levels of less than 250 watts/cm2 with suitable particle response. Our present permits treatment of a targeted tumor at a distance of up to 20 cm from the energy source, thereby allowing treatment of deep-seated thoracic tumors in humans with minimal drug involvement.
Using a larger coated delivery vehicle labeled with glucose and other moities, we are able to take advantage of a phenomena associated with the vasculature in tumor structure capillaries - large fenestrations. These fenestrations, or "holes" result in openings some 20-times larger than a health capiillary. While a normal capillary opening is about 5nm, a tumor's capillaries have large openings, usually about 100nm.
Our delivery package cannot easily pass into normal cells through ordinary fenestrations. It does pass easily, however, into a tumor capillary structure. The glucose labeling encourages a cancer cell to take the package inside the cell structure.
We are partnering with the Veterinary Oncology Group at Situs Oncology by providing the equipment and test drug for its current clinical study of magnetic hyperthermia in cats and dogs. Small animals are being treated with curative intent. The induced immunity effect observed in murine models in the Nagoya studies is under investigation to see if there is a similar response in canine and feline models.
Xenavex™
Our Xenavex™ Phase II FDA clinical trial program will initially explore the effectiveness of a nerium oleander L. derivative, oleandrin, as a potential monotherapy for mesothelioma and non-small cell lung cancer. In the near term, additional Phase II studies are planned for the purpose of exploring efficacy of Xenavex™ in treating cancer of the breast, the prostate, BRO melanoma and pediatric medulloblastoma.
Xenavex™ (NDC14213-001/01/02/03) is an ethanolic botanical extract compound of various cardioglycosides derived from oleander, a toxic plant that has been investigated and used as a "traditional medicine" for over 1,000 years. Modern oleander based drugs have previously been made in both China and Russia, where they are used as cardiology drugs. Our experience thus far is that the ethanolic extraction process results in higher ratios of the active moieties than extractions made from other processes.
Pediatric cancers, such as primitive neuroectodermal tumor (PNET) (medulloblastomas) are very difficult to treat. Even successful cases result in devastating side effects to the patient. Xenavex™ crosses the blood/brain barrier, thereby suggesting its possible use in treating pediatric brain cancers. We anticipate participating in a separate Phase II program to investigate the potential of Xenavex™ labeled with a glucose-like substance as a pediatric cancer monotherapy. The program goal is to enhance movement of Xenavex™ across the blood-brain barrier on glucose transporter (GLUT) 3 in much larger ratios than its unaugmented entry on GLUT 1 and 2.
Xenavex™ is a prescription item for its labeled indications related to cardiovascular disease. It is not approved for any other indication such as a proliferative cell disorder. In October, 2004, after extensive consideration, ShimodaAtlantic changed its pollicy regarding availability of Xenavex™ to patients seeking access to the drug under single patient investigational new drug applications (FDA Form 1571). Since then, we have provided access to the drug to qualified physicians for either investigational or "off-label" usage. It is the policy of the company to discourage off-label use of the drug and to pursue access via the FDA's single patient IND program.
In late February 2005, we obtained a NDC (National Drug Code) numerical assignment for Xenavex™ in 3ml, 10ml and 30ml packages.
Autologous Vaccine & Immune Response Stimulation
Our early-stage vaccine project is investigating whether the human immune system can be stimulated to react to, and, destroy tumor cells, based on their unique protein structure.
European investigators have reported some success in triggering the body's natural immune response to cancer cells, by introducing protein fragments similar to those created by cancer cells, but in much larger quantities than a tumor normally produces.
Our current research focuses on heat shock protein (HSP) 70, cytokeratin-19 fragments and its CYFRA-21 subunits as being potential immune system stimulators.
The investigation will seek to determine if by introducing a large amount of the protein fragments, the immune response is enhanced, thereby triggering the body’s natural defense against cell disorders.
