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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.
 

Currently, there is no other whole-animal reporter for epigenetic regulation established in any vertebrate. 

The thymus is an integral part of the adaptive immune system as it generates T cells. Its function diminishes rapidly as the body ages, leading to a compromise of the immune system in the elderly. Reconstitution of adaptive immunity through mass production of different T cell types is therefore a therapeutic need in immunocompromised populations. Furthermore, production of T cells with specific receptors targeting cancer cells is an important cancer immunotherapy approach.

Cancer cells can spread to various regions in the body in a process called metastasis which is associated with non-responsive to treatment and thus reduced survival. Identifying the markers of metastasis has been a major concern in the field of cancer diagnosis and therapy. Interestingly, research has shown that there is an increase in myeloid progenitors and myeloid cells at various stages of metastasis in an attempt by the immune system to  suppress cancer cells. This presents a promising technology for cancer immunotherapy.

Hematopoietic progenitor cells (HPC) are multi-potent hematopoietic lineage cells that can differentiate into any type of blood cell, including but not limited to erythrocytes, T cells, B cells, and natural killer cells. As such, they have high therapeutic potential in the fields of regenerative medicine and cancer immunotherapy, especially when generated from patient-derived induced pluripotent stem cells (iPSC). Currently, the most efficient protocol to produce HPCs is co-culturing human iPSCs (hiPSC) with mouse stromal cells as a two-dimensional (2D) monolayer.

Recombinant immunotoxins (RITs) constitute a promising solution to hematologic cancers (e.g., Multiple Myeloma [MM]). RITs are chimeric proteins composed of a targeting domain fused to a bacterial toxin. Upon binding to a cancer cell displaying the target antigen, RITs are internalized, metabolized and the released toxin kills the cell. While highly active and effective, current RITs have short half-lives, requiring them to be used in high concentrations for treatment. At such high concentrations, RITs may show nonspecific activity and kill healthy cells.

Cancer cells can upregulate autophagy – cell destruction – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that compounds identified by screening a library of compounds blocks autophagy in some cancer cells (e.g., melanoma) but are not toxic to normal cells. Cancer cells with mutations in the BRAF oncogene are especially dependent on autophagy. Treatment of cancer cells with the BRAF mutation can increase the efficacy of chemotherapy.

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. 

T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation.

Interleukin (IL)-34 is a homodimer that is produced mainly by keratinocytes, neuronal cells and regulatory T cells (Tregs). It is believed to play important roles in chronic inflammation and the homeostasis of microglia. Currently, there is no effective treatment for many types of retinal degeneration. An improved treatment of autoimmune uveitis is also needed, as current uveitis treatment primarily uses steroidal anti-inflammation medication, which may produce significant unwanted side effects in long-term use.