Marcela Maus | |
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Alma mater | University of Pennsylvania Memorial Sloan Kettering Cancer Center |
Scientific career | |
Institutions | Harvard Medical School |
Academic advisors | Carl H. June |
Marcela V. Maus is a professor of medicine at Harvard Medical School and director of the Cellular Immunotherapy Program at Massachusetts General Hospital. She works on immunotherapy for the treatment of cancer, using genetically engineered T cells to target malignancies (cancer).
Maus attended Stuyvesant High School in New York City. She was an undergraduate at Massachusetts Institute of Technology, where she majored in biology and literature. She earned her MD–PhD at the University of Pennsylvania, where she trained in the laboratory of Carl H. June, developing methods to expand T-cell populations, for medical therapies. She completed residency in Internal Medicine at the Hospital of the University of Pennsylvania from 2006 to 2008. She completed fellowship in Hematology and Oncology at the Memorial Sloan Kettering Cancer Center from 2008 to 2012.
In 2012 Maus returned to the University of Pennsylvania, where she became an assistant professor and director of translational medicine. Since 2015 Maus has worked in the Massachusetts General Hospital [1] and Dana–Farber Cancer Institute. Here she leads the Cellular Immunotherapy Program [2] which translates her research into clinical trials for patients with malignancies. [3] [4]
Maus develops chimeric antigen receptor (CAR)-T cells for cancer patients. [5] She demonstrated that it is possible to use engineered CAR-T cells to identify and kill tumour cells that express a specific protein, EGFR vllI (variant III). [6] She has also conducting research that examines using CAR-T cells in combination with checkpoint inhibitors could be used to treat other cancers. [7] The cells can breakthrough the blood–brain barrier, infiltrate a tumour and illicit an immune response. [6] Maus has used CRISPR-Cas9 to develop the CAR-T cells that incorporate a molecule called Bi-specific T-cell engager (BiTE). [8] Bi-specific T cell engager continues to produce short-lived molecules that attack the tumour until it is destroyed. [9] BiTEs contains two molecular arms, one which catches an antigen EGFR target on the tumour cells and the other locates a CD3 receptor of a nearby T cell. Once the target and T cell receptor are close to one another it can destroy the cancer cell. The BiTEs force the tumor and T cells together. [10] Usually BiTE is too large to cross the blood-brain barrier, but as CAR-T cells can pass through, they can produce the BiTE inside the brain. [10]
Maus is on the leadership team of MicroMedicine , a start-up which creates automated microfluidics for targeted cell isolation from biological fluids . [4] [11] Maus was awarded a Damon Runyon Cancer Research Foundation Stage 2 fellowship to develop CAR-T cells that can target abnormal antigens made from oncogenes. [9] She has turned CAR-T cells into "armoured vehicles" which can target glioblastoma brain tumours. [9]
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.
In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
Two chemically linked fragments antigen-binding form an artificial antibody that binds to two different antigens, making it a type of bispecific antibody. They are fragments antigen-binding of two different monoclonal antibodies and are linked by chemical means like a thioether. Typically, one of the Fabs binds to a tumour antigen and the other to a protein on the surface of an immune cell, for example an Fc receptor on a macrophage. In this way, tumour cells are attached to immune cells, which destroy them.
Molecular oncology is an interdisciplinary medical specialty at the interface of medicinal chemistry and oncology that refers to the investigation of the chemistry of cancer and tumors at the molecular scale. Also the development and application of molecularly targeted therapies.
Imugene Ltd is a clinical stage immuno-oncology company developing a range of new and novel immunotherapies that seek to activate the immune system of cancer patients to treat and eradicate tumours. Imugene's unique platform technologies seeks to harness the body's immune system against tumours, potentially achieving a similar or greater effect than synthetically manufactured monoclonal antibody and other immunotherapies.
Prescient Therapeutics Ltd is a clinical stage oncology company. The company is focused on the development of a universal CAR-T platform (OmniCAR), enhanced CAR-T cell manufacturing & function (CellPryme) and on two small molecule drug targeted therapies.
David G. Maloney is an oncologist and researcher at Fred Hutchinson Cancer Research Center and the University of Washington who specializes in developing targeted immunotherapies for the treatment of blood cancers.
Crystal L. Mackall is an American physician and immunologist. She is currently the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at Stanford University. She is the founding director of the Stanford Center for Cancer Cell Therapy.
Misty Rayna Jenkins is an Australian scientist known for her research into lymphocytes and cancer treatment.
Michelle Leigh Monje-Deisseroth is a neuroscientist and neuro-oncologist. She is a professor of neurology at Stanford University and an investigator with the Howard Hughes Medical Institute. She develops new treatments for diffuse intrinsic pontine glioma.
Donald M. O'Rourke is an American neurosurgeon and the John Templeton, Jr., MD Professor of Neurosurgery at the Perelman School of Medicine at the University of Pennsylvania. He graduated from Harvard University with an A.B. in Biochemistry and Molecular Biology in 1983, and attended medical school at the University of Pennsylvania where he also completed neurosurgical residency training.
Michel Sadelain is an genetic engineer and cell therapist at Memorial Sloan Kettering Cancer Center, New York, New York, where he holds the Steve and Barbara Friedman Chair. He is the founding director of the Center for Cell Engineering and the head of the Gene Transfer and Gene Expression Laboratory. He is a member of the department of medicine at Memorial Hospital and of the immunology program at the Sloan Kettering Institute. He is best known for his major contributions to T cell engineering and chimeric antigen receptor (CAR) therapy, an immunotherapy based on the genetic engineering of a patient's own T cells to treat cancer.
Epitopoietic Research Corporation (ERC) is a Belgian Pharmaceutical company that is specialized in the development of ERC1671, a treatment for Glioblastoma multiforme, which is the most aggressive form of brain cancer. In 2019 ERC provided treatment under the US Federal Right-to-try law.
Nirali N. Shah is an American physician-scientist and pediatric hematologist-oncologist, serving as head of the hematologic malignancies section of the pediatric oncology branch at the National Cancer Institute. She researches the translation of immunotherapeutic approaches to treat high-risk hematologic malignancies in children, adolescents and young adults.
Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.