3 Novel Disease-Fighting Technologies You Should Know About Ahead of BIO 2022
Researchers at the University of Chicago have developed methods to increase the clinical efficacy of immunotherapies, provide long-lasting immune tolerance for autoimmune or transplantation therapy, and treat breast and ovarian cancer with small molecules.
// FOXP3 Stapled Peptides to Deactivate Regulatory T Cells
While there have been advances in enhancing immune response to various novel therapeutics, the presence of regulatory T cells (Tregs) remains a significant challenge to clinical efficacy.
Tregs are a specialized subpopulation of T cells that act to suppress immune response, playing a critical role in preventing autoimmunity. They prevent T cells from exhibiting an immune response against the body’s antigens, including those that would normally target cancer cells.
For this reason, Treg activity can significantly limit the efficacy of immunotherapies – making a method for reducing Treg activity highly desirable for the overall advancement of the field.
Targeting the FOXP3 transcription factor, which is selectively expressed in Tregs and is necessary for Treg function, researchers today have synthesized stapled alpha helix peptides that block FOXP3 signaling, consequently inhibiting Treg function.
In initial proof-of-concept studies, the stapled alpha helix peptides bound to recombinant FOXP3 with nanomolar affinity and reduced expression of FOXP3 regulated genes.
- Lower drug resistance potential than therapeutic antibodies
- Fewer off-target effects than small molecules
- Combination therapy: (chemotherapy, radiotherapy, immunotherapy)
This research is led by University of Chicago researcher James LaBelle, associate professor of pediatrics. The research group is excited about recently completed in vivo mouse model studies for the FoxP3 project. A manuscript is pending.
The major goal of his laboratory is to dissect and pharmacologically target intracellular proteins to induce cancer cell death and manipulate the immune response. A large part of this work is focused on using portions of the actual proteins, or peptides, as drugs and biological tools to uncover specific molecular pathways in diseased and normal cells.
// Tolerizing Agonist/Immunomodulator Loaded Liposomes for Long-Lived Immune Tolerance
More than 80 diseases occur as a result of the immune system attacking the body’s own organs, tissues, and cells, according to the National Institutes of Allergy and Infectious Diseases.
The main cause of many of these autoimmune diseases is a failure of central immune tolerance: the body becomes unable to eliminate T or B lymphocytes, which produce the antibodies used to attack bacteria, viruses, and toxins.
This failure is typically driven by autoantigen specific Treg cells, and while the reasons for this failure vary, restoring proper autoantigen specific response would provide a highly effective, long-term therapy for a range of autoimmune diseases.
Taking aim at these cells, researchers have developed a method that generates antigen-specific immune tolerance for autoimmune or transplantation therapy by inducing dendritic cells with three immuno-suppressive drugs.
Used in combination with toll-like-receptor (TLR) agonists – which augment T-cell responses and downregulate suppressive effects of Tregs – a potent tolerogenic dendritic cells (tolDC) phenotype is generated, subsequently creating antigen specific Treg cells.
Today, the most effective therapies are centuries‐old drugs that have significant side effects and do not treat the root cause of the disease. And the occurrence of these diseases is increasing in the US, as per a study published in 2020 by the National Institutes of Health.
- Reliable generation of antigen-specific Tregs with minimal non-specific immune suppression
- Long-lived immune tolerance
- Easy manufacturing and storage
- Autoimmune diseases
- Transplant medicine
This work is led by Aaron Esser-Kahn, an associate professor of molecular engineering at the University’s Pritzker School of Molecular Engineering, whose research interests lie at the intersection of biology, chemistry, and materials science. His primary area of research focuses on immunoengineering and improving immune responses in vaccination.
// Novel Small Molecules for Treatment of Breast and Ovarian Cancer
The development of breast cancer is driven by the pro-oncogenic cellular activities of estrogen receptor alpha (ERα), which is overexpressed in approximately 70% of breast cancers.
For this reason, using therapies that target ERα is a leading strategy to prevent the progression or spread of breast cancer – the most common cancer in women in the US.
While acquired resistance to these therapies is a major source of breast cancer mortality, more potent antiestrogens have in preclinical models shown an ability to overcome these issues. Specifically, selective estrogen receptor (ER) degraders, or downregulators, which antagonize ERα actions and induce its degradation, have demonstrated substantial antitumor efficacy.
A promising treatment for breast cancer, in addition to ovarian cancer and osteoporosis, researchers at the University have developed a set of novel small molecules with improved therapeutic activities.
- Molecules adopt a novel orientation in protein and possess a unique scaffold compared with other antiestrogens
- Unique pharmacologic profiles
- Potential to significantly improve tissue-specific activities that are important drivers of side effects
- Breast cancer
- Ovarian cancer
// Contact Michael Hinton, Manager of Market Intelligence, who will be at BIO 2022 and can provide more detail about these technologies and others, discuss the licensing process, and connect you with the inventors.