Development of successful HIV vaccine immunogens continues to be a major challenge. Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed. The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike.
Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this. Scientists at the NCI’s Laboratory of Experimental Immunology have identified a fully human monoclonal antibody, m860, that binds to cell surface-associated Her2 with affinity comparable to that of Trastuzumab (Herceptin) but to a different epitope.
Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual''s innate and adaptive immune system to fight against specific diseases, including cancer with fewer side-effects and more specific anti-tumor activity in individual patients. T cell receptors (TCRs) and Chimeric Antigen Receptors (CARs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response to destroy abnormal cells.
Several malignancies associated with a poor prognosis such as lung, pancreatic and colorectal cancers frequently harbor constitutively active KRAS mutants, which play a pivotal role in oncogenesis. Currently, there are no potentially curative treatments against most mutant KRAS harboring cancers once they become metastatic and unresectable. Despite intensive efforts to develop potent mutant KRAS inhibitors, none have shown a significant improvement to patients.
The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.
A child's growth is dependent on the proper functioning of the growth plate, a specialized cartilage structure located at the ends of long bones and within the vertebrae. The primary function of the growth plate is to generate new cartilage, which is then converted into bone tissue and results in the lengthening of bones. Failure of the growth plate to function properly can result in short stature or sometimes a skeletal dysplasia, such as achondroplasia, in which the bones are not just short but also malformed.
One major challenge in the development of effective cancer therapies is a lack of universal, cancer specific markers in target cells. The current standard therapies rely on surgery, chemotherapy, and radiation therapy. Such procedures lead to a population of resistant cancer cells that makes further applications of chemotherapy/radiation therapy ineffective. Additionally, the systemic application of chemotherapy lacks specificity and has off-target systemic effects that lead to adverse side effects.
Scientists at NIH have identified a process to select highly tumor-reactive T cells from a patient tumor sample based on the expression of four specific T cell surface markers: programmed cell death protein 1 (PD-1; CD279), 4-1BB (CD137), T cell lg-and mucin-domain-containing molecule-3 (TIM-3), and/or lymphocyte activation gene 3 (LAG-3). After this enriched population of tumor fighting T cells, primarily tumor infiltrating lymphocytes (TIL), is selected and expanded to large quantities, it gets re-infused into the patient via an adoptive cell transfer (ACT) regimen.
Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes. NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability. For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments.
A number of factors can play a detrimental role in the process of wound healing such as poor nutritional status, smoking, various drugs, cancer, and diabetes. Wound healing impairment is a challenging clinical problem with no efficacious treatments currently available. Nitric oxide (NO) has been shown to play a role in the process of wound healing by promoting both the proliferative and remodeling phases of healing.