Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.

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. 

Despite therapeutic advances, human immunodeficiency virus (HIV) is still a pervasive disease, with approximately 37 million people infected worldwide. Peptides have become popular therapeutic agents, as these proteins offer structural diversity for many different diseases. Several peptides were commercially developed as HIV therapeutics, demonstrating the high potential for peptides in treating HIV. 

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.

Antiretroviral therapy (ART) has changed the prognosis of HIV-1 infection to a chronic illness that, in most cases, can be managed or controlled. Integrase strand transfer inhibitors (INSTIs) and reverse transcription inhibitors are essential components of ART drug cocktails. In compliant individuals, ART has been found to block viral replication completely. Additionally, blocking viral replication can prevent the emergence of drug resistance.

Chimeric antigen receptors (CARs) combine an antibody-based binding domain (and single chain fragment variable region, scFv) with T cell receptor signaling domains (CD3 zeta with a costimulatory domain, typically CD28 or 41BB). When T cells express CARs, they are activated in a major histocompatibility complex- (MHC) independent manner to kill tumor cells expressing the target to which the scFv binds.  CAR T cells targeting the B cell antigen CD19 have resulted in remissions in 60-80% of patients with pre-B cell precursor acute lymphoblastic leukemia (BCP-ALL).

Bacterial spores can be modified to display molecules of interest, including drugs, immunogenic peptides, antibodies and other functional proteins of interest (such as enzymes).  The resulting engineered bacterial spores can provide many useful functions such as the treatment of infections, use as an adjuvant for the delivery of vaccines, and the enzymatic degradation of environmental pollutants.

Research and clinical applications of induced pluripotent stem (iPS) cells are currently limited by reprogramming methods that may modify the host genome, and therefore be potentially unsafe and problematic for use in basic research, cell-based therapies, and drug-discovery applications. 

Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer.  However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer.  For those cancers associated with these limited immune systems, there remains a need for effective therapies.  Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain. 

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.