Advancements in science and technology have brought about a new wave of promising cancer immunotherapies
Guided by Science provides a platform for viewers to learn about the fundamentals of cancer immunotherapy and innovations in cancer research.
How to Treat Melanoma: Current Landscape and Options
Today, melanoma is one of the most dangerous forms of skin cancer and late-stage melanoma accounts for the vast majority of skin cancer deaths. Following diagnosis, patients are often overwhelmed by the amount of information that is available to them regarding treatment options, therapy centers, and new terminology. The treatment landscape in melanoma is constantly evolving and scientists are finding safer and more effective treatments that have long term benefits for melanoma patients. To help summarize this information, the following is a brief overview of melanoma survival rates, treatment options, and new approaches. Survival Rate Survival rates for patients in the United States vary depending on the stage of cancer and when the patient is diagnosed. For early-stage melanoma (e.g., Stage I and/or II non-metastatic), surgical excision can be curative in a majority of cases. The overall five-year survival rate for patients with such localized melanoma is 98 percent in the United States.(1) At later stages, malignant melanoma remains deadly and difficult to treat cancer. The overall five-year survival rate is 63 percent in the United States when the cancer is detected in the lymph nodes; and, declines to 16 percent when the cancer has metastasized to distant organs. Treatment Options Melanoma that has metastasized to distant organs and tissues has traditionally been treated with a combination of surgery, chemotherapy and/or radiation therapy. Numerous chemotherapy regimens have been tested in melanoma with only modest success and limited overall survival benefit.(2) Immunotherapy, which harnesses the body’s immune system to fight cancer, has been an effective treatment for patients with certain types of cancer that have been previously resistant to chemotherapy and radiation treatment, such as melanoma. The emergence of two new approaches in immunotherapy – checkpoint inhibitors and targeted kinase inhibitors – have demonstrated improvement in overall survival of patients when compared to traditional chemotherapy.(2) While immunotherapy can be extremely effective, the currently marketed therapies do not benefit the majority of patients. While checkpoint therapies can produce durable responses, 70-80% of patients do not respond to this type of immunotherapy. This non-responder population represents a large unmet medical need in oncology. A New Approach Today, scientists are working on improving immunotherapies by combining them with other types of cancer treatments to improve response rates. This combination approach may increase the number of patients that can benefit from these revolutionary therapies. Early data from clinical trials evaluating these combination approaches are promising. Researchers also continue to focus efforts on targeting pathways of various immune cell activation.(3) One such approach relies on the correlation of a type of immune cell presence in a tumor with improved prognosis and long-term survival.(4,5) This cell type, known as a CD8+ T cell, is an immune cell that can recognize and kill cancer cells. Many emerging experimental immunotherapies are seeking to increase the anti-tumor CD8+ T cell response, resulting in increased immunogenicity of the tumor. Addressing the Unmet Medical Need OncoSec Medical Incorporated is developing combination approaches for melanoma and believes to be one step closer to providing an innovative immunotherapy option for patients. OncoSec is developing immune-stimulating therapies that can convert ‘T-cell poor’ (cold) tumors to ‘T-cell rich’ (hot) tumors by driving immune cells into the tumor and stimulating anti- cancer immune activity. By increasing T-cells at the tumor site, these therapies appear to prime the immune system for improved response to checkpoint inhibitors. In OncoSec’s Phase II investigational therapy trial, ImmunoPulse® IL-12 in combination with Merck's approved checkpoint inhibitor therapy, Keytruda® (also known as pembrolizumab), showed 48% of patients with advanced melanoma had a best overall response rate in patients with cold tumors. This is in comparison to a 33% response rate with KEYTRUDA alone, typically in patients that already have hot tumors. Based on previous positive clinical data, the US Food and Drug Administration (FDA), granted OncoSec Fast Track designation. Fast Track designation is an expedited review granted by the agency to facilitate the development of drugs which treat a serious or life-threatening condition and fill an unmet medical need. Based on this designation, OncoSec is initiating a registration- directed trial focusing on patients that fail on Keytruda®, Opdivo® or combination of Opdivo®- Yervoy®. This is a Phase II, open label, multicenter study of ImmunoPulse® IL-12 in combination with a checkpoint inhibitor therapy in patients with Stage III or IV melanoma that cannot be surgically removed. OncoSec is helping to pioneer combination approaches in the melanoma space and may be the first biopharma company to receive accelerated approval to help address the large population of patients who do not respond to current checkpoint inhibitor therapies. OncoSec is hoping to improve understanding of how different therapeutics can work better together to expand the number of safer and more effective combinations. It is the team’s goal to help improve outcomes for melanoma patients and provide hope for patients suffering from late-stage melanoma. Sources 1. American Cancer Society. Cancer Facts & Figures.2. National Cancer Institute. Melanoma Treatment for Health Professionals.3. Thomas, N. E., et al. (2013). "Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study." J Clin Oncol 31(33): 4252-4259.4. Dudley, M. E., et al. (2005). "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma." J Clin Oncol 23(10): 2346-2357.5. Hunder, N. N., et al. (2008). "Treatment of metastatic melanoma with autologous CD4+ T cells against NY- ESO-1." N Engl J Med 358(25): 2698-2703.
Immunotherapy: A New Era in Cancer Care
Immunotherapies harness the natural power of our immune system to target and fight disease. Advancements in science and technology have brought about a new wave of promising cancer immunotherapies. This burgeoning field of immuno-oncology (IO) is revolutionizing how we perceive and treat cancer.
Combining Therapies to Treat Cancer
There’s never been a more exciting time for the field of cancer immunotherapy. New treatments are showing great promise and changing the way we think about cancer care. At the forefront of this revolution is the idea of combining therapies to combat the many ways cancers can adapt and survive. As our understanding of cancer and the immune system grows, we are witnessing the emergence of a new vision – where practical combinations can benefit many more patients now faced with life-threatening disease. Immune Checkpoint InhibitorsThe Foundation of Immuno-oncologyCheckpoint inhibitors work by releasing the brakes on specialized immune cells, allowing them to target and eliminate cancer. These drugs can be highly effective, as evidenced by Jimmy Carter’s recent high-profile response. Unfortunately, at this point only a minority of patients are likely to respond to these breakthrough drugs. That’s where the power of combination therapy can make a huge impact… Data suggest patients with a ‘T-cell rich’ profile are likely to respond.Immune-stimulating therapies (like OncoSec’s ImmunoPulse IL-12) have shown an ability to convert ‘T-cell poor’ tumors to ‘T-cell rich’ tumors by stimulating anti-cancer immune activity.Combining new therapies with checkpoint inhibitors may increase the number of patients that can benefit from these game-changing drugs. Combination ApproachesThe Future of Cancer CareThe promise of combination therapy is forcing researchers and regulatory authorities to rethink how we approach cancer care. The era of single therapies competing for higher response rates is seemingly coming to an end. The focus is now shifting toward understanding how therapeutics work and evaluating how different approaches can work better together to improve outcomes for patients everywhere.
New Faces of Immunotherapy
Immunotherapy is changing cancer as we know it. Experts predict that in just 10 years, immunotherapy will form the backbone for over 60% of cancer treatments, as opposed to less than 3% today.
Cancer Moonshot 2020
Cancer Moonshot 2020 is a new initiative aimed to end cancer as we know it. Led by Vice President Joe Biden, Cancer Moonshot 2020 aims to break down barriers and enable progress by enhancing data access, facilitating collaborations, and investing in the development of new technologies and treatments. While the $1 billion announced to fund this initiative is a large figure on its own, the effort will need to hyper-focus its resources and influence to make a meaningful impact. In this issue, we explore some practical ways that Cancer Moonshot 2020 can make good on its promise to improve outcomes for patients everywhere. Early DetectionThe single most important factor for a patient’s prognosis is at what stage cancer is diagnosed. For example, the 5-year relative survival rate for breast cancer is 100% at Stage I and only 22% at Stage IV. However, at least half of all cancers in the U.S. are diagnosed in stage III or IV. Cancer Moonshot 2020 could improve early detection by investing in new technologies for early detection and screening. DevelopmentThe cost to develop a new cancer drug can range from $350 million to over $5 billion in some cases. Therefore, aiding the development of new therapies will take more than just money. Cancer Moonshot 2020 can best improve new drug development by influencing regulatory agencies like the FDA to rethink how we evaluate therapeutics. Experts believe patients will benefit most from combination therapies that target multiple aspects of cancer. Thus, regulatory agencies must learn to judge the value of therapeutic in both the single-agent and combination settings. CollaborationsThe battle between cancer and the immune system is a complex mix of activity and inhibition. Thus, the key to improving patient outcomes is to combine treatments that stimulate the immune system and limit the tumor’s ability to evade immune detection. Cancer Moonshot 2020 could help by breaking down barriers to collaboration and influencing regulatory agencies to favor combination therapies. Rational combinations, like the work coming from OncoSec Medical Incorporated, have the potential to change how we treat cancer. This initiative has the power to support these approaches and do a great deal of good.
Immune System Decoding
It’s no secret that immunotherapy is changing how we treat cancer. However, this field of cancer care and the immune system are both very complicated, and scientists continue to learn more every day. In this edition of Guided by Science, we define a few key terms that are frequently lost in translation to help you better understand how the immune system works and the promise of immuno-oncology.CANCERCancer is not a singular disease. Rather, cancer describes a class of diseases in which abnormal cells can grow without control and invade other parts of the body. The result is a growth called a tumor. There are over 100 types of cancer and each case has unique characteristics. Accordingly, the idea of a single cure for cancer is not aligned with the reality of treating this class of disease. IMMUNE SYSTEMThe immune system is a network of cells, tissues, and organs that work together to protect the body from disease. To combat disease, the immune system must detect and defend against countless pathogens and distinguish these pathogens from healthy tissue. When functioning properly, the immune system has a natural ability to recognize and attack cancer cells anywhere in the body. PATHOGENPathogen is a broad term describing anything that can cause disease. The term can refer to viruses, bacteria, parasites or other potentially harmful agents. One of the main tasks of the immune system is to recognize harmful substances from the outside environment and neutralize pathogens that have entered the body. T CELLT cells are a type of white blood cell that plays a central role in the immune system to eliminate or prevent pathogens. T cell are often likened to soldiers of the immune system because they can seek out and destroy cells that are infected with germs or that have become cancerous. ANTIBODYAntibodies are proteins that the immune system uses to identify and neutralize target pathogens. Each antibody recognizes and binds to a specific antigen. This allows antibodies to tag a pathogen or abnormal cell for the immune system to see and destroy. ANTIGEN An antigen is commonly a protein produced by a cell, virus, or bacteria. In the case of cancer antigens, the protein or part of a protein is on the surface of the cancer cell that alerts the immune system. This causes the production of antibodies or creates T cells that can recognize and potentially destroy the cancer cell expressing that antigen. The immune system is a complex and essential part of the body’s survival. Immunotherapy harnesses this innate power to identify and eliminate cancer, which can use several mechanisms to evade the immune system. As the cancer treatment landscape shifts rapidly toward new immunotherapy combinations, Guided By Science is here to help you stay up-to-date every step of the way.
Melanoma is the deadliest form of skin cancer, accounting for the majority of skin cancer deaths worldwide. While melanoma rates have been rising over the last 30 years, advancements in treatment and early detection are providing new hope for patients everywhere. In this edition of Guided By Science, we explore melanoma prevention, early detection, and new treatments that are changing the way we treat this deadly disease. Prevention and Early Detection If detected early enough, surgery can be curative for many patients. The 5-year survival rate for localized melanoma (Stage I and II) in the U.S. is 98%. If melanoma advances and spreads to distant parts of the body, the 5-year survival rate falls to just 17%. These statistics underscore the extraordinary importance of understanding known risk factors and early detection guidelines. How to Lower Your Risk• Avoid indoor tanning. Tanning bed use can increase your melanoma risk by up to 75%.• Use a broad spectrum (UVA/UVB) sunscreen with an SPF of 15 or high to limit damage from sun exposure.• Limit direct sun exposure from 10:00 AM to 4:00 PM. Early Detection Tips • Examine your skin from head to toe every month so that you can find any new or changing lesions.• Learn the ABCDE rule to identify early signs of melanoma.• Schedule a professional skin exam with a physician once every year. New Treatments, New HopeThe field of immuno-oncology is fundamentally changing how we treat cancers like melanoma. Unlike traditional approaches, immunotherapies harness the natural power of the immune system to combat disease. For advanced melanoma, immune checkpoint therapies, like anti-PD-1, are quickly becoming standard-of-care. These drugs can be highly effective for a subset of patients. Unfortunately, the majority of patients will not respond to a checkpoint therapy alone. Experts believe immune-activating therapies like ImmunoPulse® IL-12 could address this great unmet need.
Taking the Fight Directly to the Tumor
Immunotherapies harness the natural power of the immune system to fight disease. Thanks to advances in science and technology, immunotherapy is fundamentally changing how we treat cancer. In this edition of Guided By Science, we explore the field of intratumoral immunotherapy, a new approach that is taking the fight directly to the tumor. What is Intratumoral Immunotherapy?Most of us are familiar with oral tablets and intravenous delivery. Unlike these systemic approaches, intratumoral immunotherapies are applied directly to the tumor. The advantage of intratumoral therapy is that it can stimulate the immune system to attack cancer while reducing the toxicities associated with systemic approaches. (Furthermore, the local aspect of the immune reaction within the tumour would be expected to reduce systemic toxicity, analogous to the use of isolated limb perfusion compared to systemic drug delivery.) Case Study: ImmunoPulse® IL-12 ImmunoPulse® IL-12 is an intratumoral immunotherapy being developed by OncoSec Medical Incorporated (NASDAQ: ONCS). OncoSec’s treatment delivers DNA IL-12 directly into tumor cells. This local treatment is designed to prime the immune system to target and eliminate cancer.
Cancer AND THE Immune System
Researchers have long questioned how tumors can grow in a healthy immune system. This question is even more important today, as immune-targeted therapies are fundamentally changing what it means to treat cancer. New evidence suggests that tumor development is heavily influenced by our immune system. This theory, termed “cancer immuno-editing,” can be broken down into three phases: elimination, equilibrium, and escape. In this edition of Guided By Science, we explore the three phases of cancer immuno-editing to understand the battle between cancer and the immune system. EliminationThroughout our lives, the immune system will encounter abnormal cells and cancerous changes. In the elimination phase, the immune system recognizes and eliminates abnormal cells before they can become advanced cancers. Elimination is carried out by tumor-specific T cells, which are immune cells developed specifically to target and attack cancer. To better understand how the immune system attacks cancer, consider the figure below. EscapeIn the escape phase, tumors use powerful adaptations to disrupt equilibrium and suppress the immune system. A common method deployed by tumors is to manipulate checkpoint pathways, which act as natural “brakes” for an immune response. As illustrated below, when checkpoint pathways like CTLA-4 or PD-1 are activated, a signal istriggered that “turns off” active T cells. Immune-Targeted TherapiesAs researchers better understand the battle between cancer and the immune system, powerful new therapies are emerging. The heart of immunotherapy research is focused on the T cell’s ability to attack and eliminate cancer. Checkpoint inhibitors that target PD-1 and other immune checkpoints are now the backbone of immuno-oncology. Many experts believe the future of cancer therapy will focus on combining checkpoint inhibitors with other therapies that activate the patient's immune system. Recent studies suggest combination therapies may be able to stop the tumor’s ability to suppress the immune system and improve a patient’s immune response.
Vaccines are designed to boost our immune system’s natural ability to protect against disease. This rationale extends to cancer therapy, where researchers are developing new treatments that direct the immune system to fight cancer. As combination therapies become the new standard in cancer care, experts believe cancer vaccines will be a critical component of the new treatment landscape. In this edition of Guided By Science, we explore the world of cancer vaccines and highlight a new approach to fight cancer with the natural power of our immune system. Preventive VaccinesCancer preventative vaccines target infectious agents that cause or contribute to cancer. They are similar to traditional vaccines, which help prevent infectious diseases, such as measles or polio, by protecting the body against infection. Most preventative vaccines are designed to stimulate the production of antibodies that protect the body from infection. Two examples of preventative vaccines are:Human papillomavirus (HPV) vaccines: High-risk strains of HPV are known to contribute to the development of certain cancers, including cervical, anal, and oropharyngeal cancers.1 Vaccines like Gardasil® and Cervarix® are approved in the U.S. to prevent HPV infection.Hepatitis B virus (HBV) vaccines: Chronic HBV infection is known to contribute to . The original HBV vaccine was the first FDA-approved preventative cancer vaccine. In the U.S. today, most children are vaccinated against HBV shortly after birth. Treatment VaccinesCancer treatment vaccines are used to treat cancers that have already developed. Treatment vaccines are designed to generate a targeted immune response against cancer. They are intended to delay or stop cancer cell growth; to cause tumor shrinkage; to prevent cancer from coming back; or to eliminate cancer cells that have not been killed by other forms of treatment. These vaccines introduce known cancer antigens to the body in order to activate T cells or induce antibody production. To be effective, cancer vaccines must achieve two goals: 1) generate an immune response against a specific cancer antigen and 2) overcome mechanisms that cancer uses to evade the immune system. As we have seen, cancer has multiple mechanisms to evade the immune system. For this reason, it has been difficult to develop effective cancer treatment vaccines. Personalized ApproachSimilar to cancer treatment vaccines, investigational therapies like ImmunoPulse® aim to stimulate the immune system against cancer. However, rather than introducing a specific antigen, ImmunoPulse® IL-12 aims to generate an anti-cancer immune response specific to each patient’s disease. In this way, therapies like ImmunoPulse® IL-12 may be able to overcome the limitations of traditional cancer vaccines. Experts believe the optimal immunotherapy will combine treatments like ImmunoPulse® IL-12 with checkpoint therapies that block the tumor’s ability to suppress the immune system.