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CD276 (also called B7-H3) is a pan-cancer antigen expressed in multiple solid tumors and an emerging cancer target. CD276 protein is overexpressed in pancreatic cancer, prostate cancer, breast cancer, colon cancer, lung cancer, and brain tumors (such as neuroblastoma) – making it an ideal target for cancer therapy. 

Investigators at the National Cancer Institute (NCI) have isolated a panel of anti-CD276 single domain antibodies (also known as nanobodies) from novel camel and rabbit single domain (VHH) libraries by phage display. 

Advanced stage cancers are typically marked by metastases of the primary cancer to secondary sites such as lungs, liver, and bones. Such metastatic cancers result in strikingly low 5-year survival rates, underscoring the need for novel therapeutics. For example, bone metastasis of primary breast cancer has a 5-year survival rate of 13%, lung cancer only 1%. There is a need for targeted therapy options specific to metastases. One approach to targeting metastases is to reduce cancer cell migration and invasion.

Prostate cancer is the most prevalent form of cancer among all men in the United States (US). It is also the second leading cause of cancer-related deaths in the US among men, largely due to the progressively treatment resistant nature of the disease. Treatment options for early stage prostate cancer include watchful waiting, radical prostatectomy, radiation therapy, and importantly androgen-deprivation therapy (ADT). Prostate cancer is dependent on androgen hormones, such as testosterone, for sustaining and promoting growth.

Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL), T cell receptor (TCR) and Chimeric Antigen Receptor (CAR) engineered T cells, or hematopoietic stem cell transplantation, is a promising new approach to cancer treatment. ACT harnesses an individual's adaptive immune system to fight against cancer, with fewer side-effects and more specific anti-tumor activity. Despite their promise of ACT as curative, these therapies are often limited by the persistence and robustness of the responses of the T cells to the cancer cells.

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and makes up 3% of all childhood cancers. Aveloar Rhabdomyosarcoma is the most aggressive subtype and is primarily established through a chromosomal translocation resulting in the fusion protein PAX3-FOXO1. Despite aggressive therapy, the 5-year survival rate for patients with high risk or recurrent Fusion Positive RMS (FP-RMS) is low (~30% and ~17%, respectively). Therefore, new therapies targeting the PAX3-FOXO1 oncogenic driver are urgently needed.  

Angiogenesis is the formation of new blood vessels from pre-existing blood vessels. Angiogenesis occurs during normal growth and development (physiological angiogenesis) and during the growth of solid tumors (pathological angiogenesis). CD276, also known as B7-H3, is a cell surface tumor endothelial marker that is highly expressed in the tumor vessels of human lung, breast, colon, endometrial, renal, and ovarian cancer, but not in the angiogenic vessels of normal, healthy tissue.

Gene therapy research has yielded FDA-approved treatments for an array of diseases. However, challenges facing nucleic-acid based therapeutics include non-specific delivery and degradation of the nanoparticles. NCI investigators have developed a solution to address these challenges in their novel nucleic-based therapy based on the conditional activation strategy. 

Hydrogels represent an attractive controlled drug-delivery system that have been used in various clinical applications, such as: tissue engineering for wound healing, surgical procedures, pain management, cardiology, and oncology. High-water content of hydrogels confers tissue-like physical properties and the crosslinked fibrillar network enables encapsulation of labile small molecule drugs, peptides, proteins, nucleic acids, proteins, nanoparticles, or cells.

Epidermal growth factor receptor variant III (EGFRvIII) is a variant of EGFR that is an excellent target for immunotherapy because of its expression in cancer cells and not in normal cells. 

Human cancers contain genetic mutations that are unique to each patient. Some of the mutated peptides are immunogenic, can be recognized by T cells, and therefore, may serve as therapeutic targets.