Research Update

2/7/17: Take a look at Ray Wong’s “Inquires with the Investigator” Piece on Placenta’s and Mesenchymal Stem Cells here

 

 12/16/2016: Take a look at Ray Wong’s “Inquires with the Investigator” Piece on Immunotherapy here

 

The PMC Research Update: October 2016

PMC Lead Researcher Raymond Wong Ph.D presented ” Harnessing the Full Potential of Immunotherapy by Targeting the Tumor Microenvironment” at the 6th International Symposium on Malignant Pleural Mesothelioma on September 34, 2016 at the UCLA Luskin Conference Center.

The PMC Research Update: March 2016

Immunotherapy for malignant pleural mesothelioma.

Immunotherapy – a class of treatments that uses the body’s own immune system to fight cancer – has increasingly gained widespread acceptance from leading biomedical scientists. There are various types of immunotherapeutic agents. In recent studies, combination immunotherapy involving different drugs was effective against melanoma and lung cancer. According to Dr. Robert B. Cameron, a professor, senior surgeon, and Scientific Adviser at the PMC, future advances in mesothelioma management will most likely involve combinations of multiple immunotherapies that work in different ways along with conventional cancer treatments like chemotherapy, radiation, and surgery.  The Pacific Mesothelioma Center is committed to testing emerging combination immunotherapy in clinical trials for mesothelioma.

microscope      Today, one of the more promising next-generation immunotherapies for cancer is mesenchymal stem cell treatment.  The in-house research program at the Pacific Mesothelioma Center is presently developing new mesenchymal stem cell-based treatments modeled on recent clinical breakthroughs in combination immunotherapy for cancer.  Mesenchymal stem cells are readily harvested from donated bone marrow, term placentas, umbilical cord blood, and fat tissue and then converted into viable biologic drugs.  These cells have been utilized in experimental treatments of inflammatory disorders and for regenerative medicine in humans.  Scientists in Germany are currently testing a new product called Agenmestencel-T in clinical trials for cancer. Agenmestencel-T is a unique, next-generation cell-based therapy composed of genetically modified mesenchymal stem cells extracted from the patient’s own bone marrow.

In clinical trials, mesenchymal stem cells have been shown to be generally safe to use in therapies for humans.  These cells appear to be a useful vector for delivering anti-cancer agents directly to malignant tumors in cancer patients in the clinic.  However, additional laboratory research is needed to determine exactly how mesenchymal stem cells can be transformed into a carrier that synergistically increases the immune-boosting properties of various other immunotherapies.  In collaboration with our scientific partners at the UCLA Comprehensive Mesothelioma Program and the West Los Angeles VA Medical Center, our in-house research program is attempting to solve this scientific enigma.  We are rigorously testing novel prototypes of mesenchymal stem cell therapies engineered to enhance immune responses against cancer.  The long-term goal of the Pacific Mesothelioma Center is to develop a wide array of mesenchymal stem cell treatments that can be scaled up for immunotherapy to fight a host of cancers.  We anticipate that someday it might be feasible to use our products in treating solid tumors, such as breast, pancreatic, and colon cancer, as well as diffuse cancers such as mesothelioma and large B cell lymphoma.

To the best of our knowledge, the Pacific Mesothelioma Center is the only research organization in the United States, perhaps the world, conducting mesenchymal stem cell research with the expressed purpose of discovering therapies and even cures for mesothelioma.  The growing potential of mesenchymal stem cells for anti-cancer immunotherapy was discussed in two recently published scientific articles (see here and here for articles) authored by two of our own researchers, Dr. Robert Cameron and Dr. Raymond Wong, and their collaborators.  These research papers explore recent studies on immunotherapy for cancer, including innovative immunotherapy approaches that our own scientists are investigating in our laboratory facilities at the Pacific Mesothelioma Center.

Blood-based detection of mesothelioma.

An exciting new lab test for potentially detecting mesothelioma before clinical symptoms appear is now on the horizon.  A recent study by Australian researchers demonstrated that a blood-based test might accurately detect mesothelioma 4-10 years in advance of clinical diagnosis.  This new test relies on detecting a marker called ENOX2 in the blood.  Specific variations of ENOX2 appear to be present in the blood of asbestos-exposed individuals many years in advance of actually developing mesothelioma.  While this test still requires rigorous follow-up studies to validate its accuracy, it could someday be a powerful new tool for oncologists to monitor individuals at highest risk for developing mesothelioma.  This test could also be a useful, non-invasive method for closely monitoring mesothelioma surgery patients – who are inherently at high risk of relapsing after tumor resection.

Researchers at the Pacific Mesothelioma Center are now embarking on an ambitious collaboration with partners in the field to rigorously evaluate the clinical utility of ENOX2 detection in the blood of mesothelioma patients.  Since 2015, the Pacific Mesothelioma Center has worked closely with colleagues at UCLA to establish a comprehensive repository of tissue specimens collected from mesothelioma patients.  This inventory includes frozen blood specimens collected from mesothelioma patients at pivotal time points during their treatment.  Our researchers are now strategically positioned to leverage this crucial resource for advancing the development of this promising new lab test.

 

 

PMC Research Update: December 2015

 

Pacific Mesothelioma Center - immunotherapyOver this past year we have seen tremendous strides made in the area of mesothelioma and immunotherapy research. . A new immunotherapy drug that targets malignant pleural mesothelioma has shown promise in early trial results. In less than six months, tumors shrunk in nearly 75% of participants receiving this experimental medication. Mesothelioma is a rare cancer that affects the pleura – a thin membrane lining the lungs and chest wall. It is mainly caused by long-term overexposure to asbestos. This disease is less common than solid tumors like lung, breast, and prostate cancers, but millions of Americans who once worked in asbestos-laden environments, such as military bases, shipyards, and textile manufacturing plants, are still at risk for developing mesothelioma as they age. The need for life-extending treatments, and ideally a cure, is more imminent than ever. The Pacific Mesothelioma Center (PMC), under the auspices of the Pacific Heart, Lung & Blood Institute (PHLBI), is proud to be on the forefront of the search for cutting edge medical solutions  – including immunotherapy –  to combat this devastating disease. The PMC’s mission is to help find a cure for mesothelioma and to improve the quality of life of patients and their families affected by this condition.

Immunotherapy

Unlike the large university medical schools sponsoring the new immunotherapy drug trial, the PMC is a small nonprofit research center staffed by a limited number of dedicated, highly qualified scientists and administrators. With a laser-focused strategy, we are continuing to build on our in-house accomplishments in cancer research. Immunotherapy – a class of treatments that uses the body’s own immune system to fight cancer – has increasingly gained widespread acceptance from leading biomedical scientists. There are various types of immunotherapeutic agents. In recent studies, combination immunotherapy involving different drugs was effective against melanoma and lung cancer. According to Dr. Robert B. Cameron, a professor, senior surgeon, and Scientific Advisor at the PMC, future advances in mesothelioma management will most likely involve combinations of multiple immunotherapies that work in different ways along with conventional cancer treatments like chemotherapy, radiation, and surgery. The Pacific Mesothelioma Center is committed to testing emerging combination immunotherapy in clinical trials for mesothelioma.

Mesenchymal Stem Cell Treatment

Today, one of the most impressive immunotherapies for possibly eradicating cancer is mesenchymal stem cell treatment. The in-house research program at the Pacific Mesothelioma Center is presently developing new mesenchymal stem cell-based treatments modeled on recent clinical breakthroughs in combination immunotherapy for cancer. Mesenchymal stem cells are readily harvested from donated bone marrow, term placentas, umbilical cord blood, and fat tissue and then converted into viable biologic drugs. These cells have been utilized in experimental treatments of inflammatory disorders and for regenerative medicine in humans. Scientists in Germany are currently testing a new product called Agenmestencel-T in clinical trials for cancer. Agenmestencel-T is a unique, next generation cell-based therapy composed of genetically modified mesenchymal stem cells extracted from the patient’s own bone marrow.

 

Stem Cells 20X magnificationIn clinical trials, mesenchymal stem cells have been shown to be generally safe to use in therapies for humans. These cells appear to be a useful vector for delivering anti-cancer agents directly to malignant tumors in cancer patients in the clinic. However, additional laboratory research is needed to determine exactly how mesenchymal stem cells can be transformed into a carrier that synergistically increases the immune-boosting properties of various other immunotherapies. In collaboration with our scientific partners at the UCLA Comprehensive Mesothelioma Program and the West Los Angeles VA Medical Center, our in-house research program is attempting to solve this scientific enigma. We are rigorously testing novel prototypes of mesenchymal stem cell therapies engineered to enhance immune responses against cancer. The long-term goal of the Pacific Mesothelioma Center is to develop a wide array of mesenchymal stem cell treatments that can be scaled up for immunotherapy to fight a host of cancers. We anticipate that it may someday be feasible to use our products in treating solid tumors, such as breast, pancreatic, and colon cancer, as well as diffuse cancers such as mesothelioma and large B cell lymphoma.

 

To the best of our knowledge, the Pacific Mesothelioma Center is the only research organization in the United States, perhaps the world, conducting mesenchymal stem cell research with the express purpose of discovering therapies and even cures for mesothelioma. The growing potential of mesenchymal stem cells for anti-cancer immunotherapy was discussed in two recently published scientific articles authored by two of our own researchers, Dr. Robert Cameron and Dr. Raymond Wong, and their collaborators. These research papers explore recent studies on immunotherapy for cancer, including innovative immunotherapy approaches that our own scientists are investigating in our laboratory facilities at the Pacific Mesothelioma Center.

Goals for Our Research Going Into 2016

One of our goals is to impact the rapidly evolving field of research on mesenchymal stem cells and immunotherapy for cancer. We can achieve this goal by continuing to take methodical, evidence-based steps that allow us to move well-designed experimental treatments from the bench to the bedside. Doing this, however, requires sufficient funding. Scientific research is an arduous and time-consuming process that can never be rushed. Nevertheless, we have made significant strides in the last few years, successfully translating our concept, or hypothesis, about the anti-cancer benefits of mesenchymal stem cells into a proof of concept. As we generate new data through ongoing research, we are now closer than ever to expanding our laboratory studies that can pave the way for next-generation clinical trials.

 

 

Pacific Mesothelioma Center Research Update: October 2015 

Immunotherapy, which uses the body’s immune system to fight cancer, is now an accepted fourth type of cancer treatment in addition to surgery, chemotherapy and radiation. Immunotherapy works by stimulating patients’ own immune systems to attack cancer cells or by eliminating specific cancer mechanisms that allow cancer cells to evade the immune system. For the first time ever, we are seeing real benefit of immunotherapy for malignant pleural mesothelioma.
The Pacific Mesothelioma Center believes that the future of mesothelioma treatment will involve combining multiple immunotherapies that work in different ways with more traditional cancer treatments, like surgery. In fact, combination immunotherapy with the FDA-approved drugs nivolumab + ipilimumab has already been shown to be effective against melanoma and lung cancer. The Pacific Mesothelioma Center is dedicated to bringing similar combination immunotherapy into clinical trials for mesothelioma.

Numerous compounds with immunotherapeutic potential have been identified. PMC’s research is focused on creating a repertoire of immunotherapies by genetically engineering mesenchymal stem cells to deliver these compounds more specifically towards tumor tissue. This approach would theoretically enhance the potency of these immunotherapeutic compounds in tumors while minimizing exposure of normal tissues, thus minimizing toxic side effects.

 Pacific Mesothelioma Center Research Update: February 2015

Immunotherapy is the most significant recent breakthrough for treating cancer. The successful commercialization of immune checkpoint inhibitors ipilimumab and nivolumab demonstrates that the immune system can be effectively activated to control tumors and extend the lives of a select proportion of cancer patients. However, the majority of cancer patients treated with immune checkpoint inhibitors do not respond to treatment. Immunologists have long hypothesized that tumor tissue often harbors multiple resistance mechanisms that can reduce the effectiveness of immunotherapy. Reversing this immunological resistance in tumors could potentially extend the therapeutic reach of currently-available and also future immunotherapies.

Researchers in the field are exploring diverse strategies to reverse immunological resistance in tumors. Pacific Mesothelioma Center Scientific Researcher, Raymond Wong, Ph.D., has been working to engineer universally compatible stem cells that hold potential for altering immune resistance in solid tumors such as mesothelioma. Such approaches can be readily evaluated using complex three-dimensional tumor cell models that simulate human tumor tissue in the laboratory.

3D_Tumor

Pictured: Human tumor cells (green) grown in three-dimensions and visualized under a microscope. Such models are being used at the Pacific Mesothelioma Center to test the potency of novel anti-tumor treatments.

 

 

 

 

 

 Pacific Mesothelioma Center Research Update: December 2014

Mesenchymal Stem Cells

In 2014, the Pacific Mesothelioma Center continued research on harnessing the potential of mesenchymal stem cells (MSCs) for cancer therapy.  MSCs are a unique type of cell isolated from fat tissue, bone marrow, cord blood and placenta.  Dr. Raymond Wong presented research data on strategies to engineer MSCs to deliver cancer-fighting biological molecules.

Patient-Derived Mesothelioma Tissue Analysis 

Dr. Irina Ianculescu generated exciting data regarding the unique gene expression profile of patient-derived mesothelioma tissue.  This data is guiding the continued development of 3-dimensional tumor models used to rapidly test potential cancer-fighting therapies and speed translation of promising
agents into human clinical trials.

Cryoablation (Freezing)

The Pacific Mesothelioma Center continued its pioneering work in MPM cryoablation through
our partnership with Dr. Warren Grundfest in the Biophotonics Laboratory of the Department of Bioengineering and UCLA’s Henry Samueli School of Engineering. This work utilized PMC’s own thermal camera to design the world’s first intra-operative MPM cryosprayer and model the effects of this innovative freezing technology on the treatment of MPM.  Our long-term goal is to advance combination cryoablation and immunotherapy regimens for treating MPM.

 Pacific Mesothelioma Center Research Update: May 2014

Immunotherapy to treat mesothelioma:

February 2014

 Pacific Mesothelioma Center  Research Update:

Stem Cells 20X magnificationIn 2013, PMC scientists Drs. Raymond Wong and Irina Ianculescu launched a much anticipated research project involving the use of adult stem cells for tumor-targeted delivery of immunotherapeutic proteins. These specialized stem cells, called mesenchymal stem cells, are found in a variety of tissues, i.e. bone marrow, fat, umbilical cord blood, and term placenta. Scientists have recently found that mesenchymal stem cells can be easily harvested from human placentas, which are typically discarded post-delivery and this observation has opened a new chapter in stem cell medicine.

Placental-derived mesenchymal stem cells are intriguing because they, like the placenta organ itself, are not easily recognized by the body as foreign tissue. This makes them an excellent source of universally-compatible stem cells for use in cancer therapy. Modified mesenchymal stem cells can serve as a vehicle for delivering a wide range of molecular and gene therapies directly to the site of cancer, and may be particularly useful in mesothelioma and other solid tumors in the chest. Our scientists plan to test the effects of modified mesenchymal stem cells on multicellular tumor spheroids – a custom designed 3-D model for studying tumor responses in vitro.

May 2013 

 Pacific Mesothelioma Center Research Update:

PMC research scientists Drs. Raymond Wong and Irina Ianculescu are currently developing a novel experimental system that holds promise for improved modeling of human pleural mesothelioma tumors in tissue culture plates.  This system mimics the complex 3-dimensional structure of solid tumors without using research animals, which is becoming less acceptable in medical research.  By using this model, they are investigating the unique gene expression profiles of human pleural mesothelioma cells, i.e., the abnormal increase or decrease of genetic signals in cancerous cells versus normal cells.  By studying these highly regulated signals, we hope to gain further insight into the specific genetic changes that lead to mesothelioma and its frequent resistance to radiation and chemotherapy.  This information may allow us to elucidate a particular genetic signature of pleural mesothelioma, allowing for identification of individuals who are at high risk for developing this dreadful disease.  3-dimensional culture models of human pleural mesothelioma will also be useful for optimizing novel therapies, such as cryotherapy and immunotherapy.

PMC is also continuing to work in collaboration with the University of Pittsburgh, University of Pennsylvania, Mt. Sinai, New York University, and the Heat and Frost Insulators Union to establish a west coast repository of high quality, asbestos-related tumor tissue specimens and fluid samples from pleural mesothelioma patients.  This repository will be used to catalyze research into developing new diagnostic tests for earlier detection of the disease.

At the UCLA Department of Bioengineering, Drs. Warren Grundfest and Marko Kostic are continuing to develop a prototype cryosprayer designed to safely deliver liquid nitrogen into the chest cavity of mesothelioma patients undergoing surgery.  This initiative is based on data recently presented by Drs. Robert Cameron and Dongmei Hou of the UCLA Punch Worthington laboratory, where they demonstrated that human pleural mesothelioma cells are particularly sensitive to freezing.  Using liquid nitrogen to carefully freeze a thin portion of the chest wall surface after surgically removing all visible mesothelioma tumors may potentially destroy residual tumor cells, thereby reducing the chance of disease recurrence in patients.

May  2013 

UCLA Bioengineering Research Update:

Cryotherapy System-The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering is continuing development of a novel cryotherapy system for intraoperative treatment of mesothelioma.  This project is based on the work by Dr. Robert B. Cameron at the Pacific Mesothelioma Center which has shown that mesothelioma cancer cells are sensitive to cold.  The research in Biophotonics laboratory explores the potential use of liquid nitrogen as means to reduce or eliminate the remaining cancer cells that cause recurrence of mesothelioma after the resection.  More information will be shared at the 3rd International Symposium.

The researchers have developed initial computer models that predicted depth and temperature of freezing during therapy.  Presently, researchers are working on expanding computer simulations to include more complex anatomical and physiological models.  These new simulations will enable better understanding of the impact that blood flow and bone have on the temperature profile of tissue, as well as how different blood flow rates and liquid nitrogen treatment times affect the tissue temperature.  Work on developing algorithms for the optimal dose of liquid nitrogen is also continuing.

This extramural grant has been funded by Pacific Mesothelioma has also enabled UCLA to progress in developing a novel cryo sprayer system.  After conducting several bench top tests of the system, an improved liquid nitrogen dispensing module was designed and fabricated.  Currently, engineers are designing a distal end that will accommodate the new module and additional tests are planned for the very near future.

November 2012

 Pacific Mesothelioma Center Research Update

Scientists at the Pacific Mesothelioma Center (PMC) are developing novel methods for creating and studying mesothelioma tumors outside of the human body, in order to more efficiently and accurately test the effectiveness of promising new treatments.  By combining human mesothelioma cells, connective tissue (stroma), and immune cells in culture dishes, our researchers can create small, nodule-like structures called “spheroids.”  These spheroids appear nearly identical to the mesothelioma nodules that typically are found on the lining of the chest cavity in patients with this disease.  Many potential therapies, including immunotherapy and others, are so complex that the optimal conditions necessary for successful therapy cannot be defined easily, but require testing literally hundreds of different conditions – something that is not possible in standard research models.  Our tumor spheroid model now makes such testing possible; consequently speeding the translation of basic research into clinical therapy for mesothelioma patients.

PMC scientists also are beginning to study gene expression in mesothelioma cells; that is, the extent to which certain genetic signals are abnormally increased or decreased compared to normal cells.  Cell growth and death is highly regulated by genetic signals, and a better understanding of the specific genetic changes that occur in mesothelioma cells will give us insight into what causes these cells to grow and divide uncontrollably.  Furthermore, the specific genes involved may provide a characteristic genetic profile or signature, which may be used to identify individuals who are at particularly high risk for developing mesothelioma even years before it occurs.  Such knowledge would allow treatments to be tested that potentially could prevent the disease altogether.

November, 2012

UCLA Bioengineering Research Update:

The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering continues to develop a unique tool to aid in the treatment of Mesothelioma.  This research effort takes advantage of the fact that mesothelioma is sensitive to freezing.  Work by Dr. Robert B. Cameron and others has shown that freezing can successfully treat local chest wall mesothelioma recurrences.  But to date there has been no practical instrumentation to apply this technology at the time of resection of primary tumors.

Work in the Biophotonics laboratory is developing instrumentation to effectively apply the cryogenic coolant (liquid nitrogen) to freeze mesothelioma.  Additional studies are developing algorithms to determine the optimal dose of liquid nitrogen.  This technology will be applied in an effort to reduce mesothelioma recurrence after primary resection in the hope that the freezing technique will help kill residual mesothelioma cells.

Funding from the Pacific Mesothelioma has also enabled engineers and scientists at UCLA to work on the development of computer models which predict the depth and temperature of freezing during therapy.  Validation of these computer models is the subject of current research.  Eric Jung, undergraduate mechanical engineering student, and James Garritano, graduate Bioengineering student, have joined the project to work with these sophisticated computer tools.

August 2012

UCLA Bioengineering Research Update:

The Biophotonics Laboratory in the Department of Bioengineering, directed by Professor Warren S. Grundfest, M.D., FACS, at the UCLA School of Engineering has initiated the development of a unique tool to aid in the treatment of Mesothelioma.  This tool uses cryogenic fluid chilled to -196ºC to rapidly freeze mesothelioma cells that remain after surgical resection or when they occur as superficial recurrences on the chest wall.  Investigations will focus on the use of this cryo therapy technology to reduce or eliminate the cancer cells in effort to prolong life.  The support from the Pacific Mesothelioma Foundation has allowed Dr. Grundfest to acquire and build a uniquely designed instrument called a CryoSprayer that allows for controlled delivery of a cryogenic fluid during surgery or during treatment for post-surgical superficial chest wall occurrences.  Liquid nitrogen serves as a cryogenic fluid because it rapidly freezes the surface and then evaporates producing a thin layer of frozen tissue.  Protecting the vital structures but ensuring the complete treatment of lesions is necessary before clinical trials can begin.

Funding from Pacific Mesothelioma has also enabled engineers and scientists at UCLA to work on the development of computer models which predict the depth and temperature of freezing during therapy.  Validation of these computer models is the subject of current research.  An additional UCLA graduate student and an undergraduate student have joined the project to work with these sophisticated computer tools.

 August 2012

  Pacific Mesothelioma Center Research Update:

We recently launched a 3-dimensional in vitro (cultures in petri dishes) tumor model (3DTM) program for better assessment of potential mesothelioma therapies.  Evidence is mounting that these 3DTM’s more accurately reflect the complex tumor microenvironment in vivo (in animals/people) than traditional 2-dimensional “monolayer” culture models. This is particularly true with respect to gene expression, signaling pathways, cellular metabolism, and drug sensitivity.  3DTM will allow for more rapid and cost-effective testing of potential anti-tumor agents, including immunotoxins, cytokines, chemokines, gene-modified stromal cells, and anti-angiogenic compounds. Such improvement in testing candidate compounds promises to provide quicker “proof-of-concept” data and lead to earlier clinical trials for mesothelioma patients.
PMC also in on the verge of launching its mesothelioma screening project. This program will evaluate a variety of tests designed to identify individuals who have been exposed to asbestos and specifically those who are at risk for developing mesothelioma. Identification of people likely to develop this fatal disease would allow prophylactic pleural-ablative interventions to be used to prevent the disease altogether.