RNA nanoparticles have the potential to serve as excellent drug or imaging delivery systems due to their designability and versatility. Furthermore, the RNA nanoparticles of the invention are also capable of self-assembly and potentially form nanotubes of various shapes which offer potentially broad uses in medical implants, gene therapy, nanocircuits, scaffolds and medical testing.
Current treatments for cancer and viral infection are limited remedies that often suppress cell or viral replication rather than eliminate diseased cells entirely from the body. A further limitation is that these therapies often compromise healthy cells as well, leaving problems of recurrence and side effects.
Researchers at developed a novel therapeutic nanoparticle (NP) system harboring therapeutic small siRNA that can significantly enhance effectiveness and specificity of treatments by killing diseased cells.
Nanoparticles such as lipid-based nanoparticles (LNPs) represent a relatively new era of targeted drug delivery systems wherein these biocompatible particles can carry the drug(s) of interest to a specific tumor site. The new generation of nanoparticles, known as stealth nanoparticles, are engineered to have a coating of polyethylene glycol polymer (PEG) or other glycolipids that enable them to evade the immune system and have a longer circulation lifespan as well as improved bioavailability to diseased tissue and reduced non-specific toxicity.
B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes. Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST). However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients. Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.
The manner by which cancers evade the immune response is not well-understood. What is known is that the manner is an active process that regulates immune responses employing at least two types of suppressive cells, myeloid-derived suppressive cells and regulatory T cells (Tregs), a key subset of CD4+ T cells that controls peripheral tolerance to self- and allo-antigens. Tregs are considered to play a key role in the escape of cancer cells from anti-tumor effector T cells.
Regulatory B-cells (Breg) play an important role in reducing autoimmunity and reduced levels of these cells are implicated in etiology of several auto-inflammatory diseases. Despite their impact in many diseases, their physiological inducers are unknown. Given that Bregs are a very rare B-cell, identifying factors that promote their development would allow in vivo modulation of Breg levels and ex-vivo production of large amounts of antigen-specific Bregs to use in immunotherapy for auto-inflammatory diseases.
Immortalization of plasma cells leads to plasma cell malignancy diseases such as multiple myeloma (MM). B-cell maturation antigen (BCMA) is a protein that is preferentially expressed by malignant and normal B cells and plasma cells, butnot on other cells in the body. This limited expression profile suggests that BCMA is a promising target for anticancer therapeutics for cancers in which there is excess production of plasma cells and B cells.
Targeting the CD22 receptor of B-cells with chimeric antigen receptor (CAR)-T cells has been a promising new therapy to treat B-cell malignancies in clinical trials, inducing remission in 70% of patients with relapsed acute lymphoblastic leukemia (ALL). However, diminished CD22 expression on B-cell surface can lead to relapse and decreased remission duration, which may be prevented through increasing CAR-T affinity towards CD22.
Patients with chemotherapy-refractory, diffuse large B-cell lymphoma (DLBCL) have poor prognoses. CD19 and CD20 are promising targets for the treatment of B-Cell malignancies. However, despite the initial promising results from anti-CD19 CAR therapy, only 30-35% of patients with DLBCL achieve remissions lasting longer than 2-3 years after anti-CD19 CAR T-cell therapy. Relapse and non-response are likely due to diminished CD19 expression after anti-CD19 therapy and low expression of CD19 in some lymphomas.
CD22 is a common cell surface glycoprotein expressed in B-cells and present in B-cell lymphomas; e.g., hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL), chronic lymphoblastic leukemia (CLL), and other cancers. It is therefore a target for cancer immunotherapy. Conjugation of anti-CD22 monoclonal antibodies with toxins or drugs has shown promise in clinical trials. However, all monoclonal anti-CD22 antibodies used in clinical trials are of murine origin.