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Memorial Sloan Kettering Cancer Center to study photodynamic therapy for multiple tumor types
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Researchers at Memorial Sloan Kettering Cancer Center have initiated several studies to assess photodynamic therapy for patients with prostate, esophageal, breast and bladder cancers.
The new research has received substantial independent funding to support translation into clinical trials, according to urologic surgeon Jonathan A. Coleman, MD.
Coleman has spent the past several years studying the novel therapy and will help lead these clinical trials with colleagues Hans Gerdes, MD; Susan Slovin, MD, PhD; and Komal Jhaveri, MD.
HemOnc Today spoke with Coleman about how the research will unfold, as well as the potential of this treatment modality for patients with cancer.
Question: What is photodynamic therapy?
Answer: The technology involves a compound derived from the naturally occurring agent chlorophyll, found in plants and bacteria. It was synthesized by professors Avigdor Scherz and Yoram Salomon at Weizmann Institute of Science, and devised as a biologic therapeutic specifically to treat cancer. The story behind it is quite touching. One of the scientists had a family member who developed cancer and wanted to do what he could to help her. He knew how plants use naturally occurring substances to fight off pathogens and, with his research team, they discovered ways that a form of chlorophyll could be used in this way. The researchers synthesized a chlorophyll agent in the laboratory and found ways to activate it using light. The agent was then manufactured by Steba Biotech into a substance that can be safely used in animals and humans. The agent — known as WST11, or Tookad Soluble — is administered intravenously. It circulates harmlessly through the body, traveling through the vascular system, and is cleared from the body in a few hours. When it encounters a certain wavelength of light in the near infrared range, it becomes activated and generates extremely short-acting free radicals that act locally to specifically destroy the blood vessels that feed the tumor cells and the tumor cells directly, leading to a complete tumor death within hours after treatment. The light can be delivered to tissues in a few different ways, though typically we use laser fibers inserted into the tissues or cavities to achieve localized ablation effects. This treatment is called vascular-targeted photodynamic therapy (VTP). It has very little impact on surrounding healthy tissues and structures when they are not exposed to light. Luckily, the scientist’s family member recovered and did not need this therapy, but the agent went on to be developed and commercialized. This agent has been used to treat cancers in patients through a series of clinical trials, including a study of men with prostate cancer that showed the treatment was safe and effective in eradicating Gleason 6 prostate cancer and had very little in the way of side effects, such as urinary or sexual dysfunction. Compared with men on active surveillance, there was an impressive reduction in the subsequent chance of finding higher-grade cancers in men who received VTP treatment, apparently decreasing the risk of Gleason 7 or higher cancer on subsequent biopsy at 2 years by roughly half. Though initially used against prostate cancer, there is interest in using the treatment against a variety of different malignancies. Our group at Memorial Sloan Kettering has been working in a collaborative effort with the Weizmann Institute to develop new ways to use the treatment.
Q: What will your research assess?
A: We are launching four different trials within the next several months in patients with prostate, bladder, esophageal and breast cancers. About 6 years ago, we began a collaborative research project initially supported by an independent research grant from The Thompson Family Foundation. This foundation gave us a unique opportunity to bring outstanding researchers from Weizmann Institute and Memorial Sloan Kettering together to study how VTP therapy can be used to treat several different types of cancers. This opportunity accelerated our work dramatically and helped us to develop methods to utilize this therapy by itself and also in combination with a variety of drugs to augment its effect not only for localized cancers, but also potentially in metastatic cancers. Our current group of trials is part of this program to look at the effects of Tookad VTP in patients with advanced esophageal and breast cancer, and the localized effects in prostate and forms of bladder cancer. In addition to the clinical benefits we expect to see, we are very interested in evaluating the biological effects of this treatment in tumors and normal tissues and are collecting specimens that will be analyzed in the lab. We have plans for other trials that will be informed by the results of these initial studies.
Q: When are the anticipated timelines of the studies?
A: The esophageal trial has received review and approval by the FDA and our Institutional Review Board (IRB), and we are nearly ready to start enrolling patients. In fact, we just received the clinical devices to treat patients and the drug shipments have also arrived. The trial we have for prostate cancer is for men with Gleason 7 (3+4), predominantly unilateral tumors. It was also approved by the FDA and just approved by the IRB. We are now working with Steba Biotech to establish the start time for that trial, but we anticipate being able to start treating patients within the next month or so. The breast cancer trial we have arranged as a collaboration between Memorial Sloan Kettering, Steba Biotech and Merck. We are going to be combining the therapy with pembrolizumab (Keytruda, Merck) to treat certain types of breast cancer. This trial is now with Merck, where they are reviewing and working on the final details of the trial. We anticipate this trial to open within the next 4 to 6 months. Our bladder cancer trial addresses a form of bladder cancer that affects the kidneys. This study is now starting the IRB approval process and we hope to start treating patients by the summer. We have trials in process for treating advanced prostate and esophageal cancer that will also be combined with pembrolizumab and other agents where we have seen complementary activity in the lab.
Q: What is the potential of this treatment approach?
A: I have spent the past several years studying this therapy in the lab with our research team at Memorial Sloan Kettering, led by Kwanghee Kim, MD, and have seen its tremendous potential. Unlike other forms of tumor ablation techniques, this therapy allows us to treat tumors that can be present in sensitive parts of the anatomy, without damaging those areas, including major blood vessels and neurovascular structures. It is a nonthermal therapy that does not damage tissue collagen and maintains tissue integrity. We have shown that there are numerous places in the body where the therapy can be used very safely without serious toxic side effects that would be seen with other forms of treatment. Another thing we find interesting is the therapy delivers its effect. If there are blood vessels nearby when we use other types of ablative therapies, those blood vessels hinder treatment effects. However, in the case of VTP therapy, the blood vessels actually deliver and enhance the effect. The final thing that we find very interesting is that there appears to be a very strong immune response that occurs in reaction to this therapy, and this is why we are interested in using it along with other therapies to augment the effects of immunotherapies and potentially promote a selective antitumor immune response. All of these things together make this a very promising therapy and an innovative and novel approach to treating cancer.
Q: Why were the four specific cancer types chosen?
A: Our preclinical work in the lab has been focused on difficult cancers for which we need better therapies that are effective and less harmful. One of the reasons we chose to test photodynamic therapy in hollow organs — such as the bladder, ureter and esophagus — is because these are areas that we cannot normally treat from the inside without damaging the organ and its function. There are major limitations in terms of the types of therapies we can use to treat tumors inside of an organ or near major blood vessels other than removing the entire organ. Treatments for prostate and breast cancer can also be highly debilitating. Studies in prostate cancer so far have shown effective eradication of cancer within the gland, while men can maintain their normal function. Finally, these cancer types share similarities to many other types of cancer, and we hope to learn from these studies on how we can apply VTP therapy effectively in many other cancers.
Q: Is there anything else that you would like to mention?
A: A lot of the work we have done would not have been possible without the support of The Thompson Family Foundation. This is a dynamic time in medical research where biotechnology tools allow for incredible insight and advances to be made, yet funding for research is extremely limited, especially for independent development of novel and innovative therapies. However, there is a compelling and critical need for this type of work, so it is incredibly helpful when private funders help to propel technology like this one forward. Our research consortium focused on VTP includes Memorial Sloan Kettering, Weizmann Institute and now Oxford University. The collaboration has been very open in exchanging information between our research teams with individual labs working closely together in partnership. We are very excited as we are now embarking on an additional project, also supported by The Thompson Family Foundation, which will enable us to study VTP therapy in pancreatic cancer for the first time. This project is a collaboration between Memorial Sloan Kettering, Weizmann Institute and Cold Spring Harbor Laboratory. We are all so very thrilled to see the VTP sphere expanding, and the game-changing possibilities it represents. – by Jennifer Southall
For more information:
Jonathan A. Coleman, MD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: odonnele@mskcc.org.
Disclosure: Coleman reports no relevant financial disclosures.