Broadly Neutralizing Human Anti-HIV Monoclonal Antibody 10E8 and Related Antibodies Capable of Neutralizing Most HIV-1 Strains

The uses for human anti-HIV monoclonal antibody 10E8 and its variants include passive immunization, therapeutic vaccination, and the development of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing antibodies isolated and it neutralizes up to 98% of diverse HIV-1 strains. 10E8 is specific to the membrane-proximal external region (MPER) of the HIV envelope protein gp41 and 10E8 is orthogonal to other anti-HIV antibodies. In combination with other antibodies 10E8 may provide an antibody response that neutralizes nearly all strains of HIV-1.

HLA-class II-restricted T Cell Receptors for PIK3CA “Hotspot” Mutations, E545K and N345K

Summary: 

The National Cancer Institute (NCI) seeks co-development partners and/or licensees for a collection of T cell receptors (TCRs) that specifically target PIK3CA mutations to treat patients with tumors expressing these mutations in the context of HLA-DPA1*01:03:01, HLA-DPB1*04:01:01 or HLA-DRB1*04:01.

Description of Technology:

Next-Generation 5-HT-2B Serotonin-Receptor Antagonists for Anti-Fibrotic & Cardiopulmonary Therapy

This technology includes a family of small-molecule antagonists that selectively block the 5-HT2B serotonin receptor—an upstream driver of tissue-remodeling—to address fibrotic, cardiopulmonary and related disorders. Built on a conformationally-locked “(N)-methanocarba” nucleoside scaffold, the compounds show nanomolar potency, >30–400-fold selectivity over the closely related 5-HT2C receptor, and favorable oral bioavailability in rodents.

Optimized Monospecific or Bicistronic Chimeric Antigen Receptor (CAR) Constructs Targeting CD19 and CD20

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. 

Combination of recombinant IL-7 with Chimeric Antigen Receptor (CAR) T Cells Targeting Glypican-3 (GPC3) for the Treatment of Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. standard treatment for HCC is not suitable for a large proportion of liver cancer patients. As a result, alternative treatments are needed. Chimeric antigen receptor (CAR) T cell therapy is a promising alternative approach selectively targets targeting tumors via tumor-specific antigens. However, to date, no effective CAR T cell therapy exists for HCC. 

Single Domain Antibodies Targeting the S2 Subunit of SARS-CoV-2 Spike Protein

The COVID-19 pandemic is a worldwide public health crisis with over 100 million confirmed cases and 2.4 million deaths as of February 2021. COVID-19 is caused by a novel coronavirus called SARS-CoV-2. Almost all the neutralizing antibodies targeting SARS-CoV-2 that are in development recognize the receptor binding domain (RBD) on the spike (S) protein. Blocking the interaction of RBD and the ACE2 receptor on human cells is the first of the two critical steps for neutralization of the virus.

Use of VDAC inhibitor, VBIT4, as a Treatment for Lupus

This technology includes a small molecule drug (VDAC inhibitor, also known as VBIT4) that may be useful for inhibiting lupus disease. To test lupus animal model, VBIT4 was continuously administered for 5 weeks to mice and there was no mortality or clinical symptoms in these animals. Additionally, VBIT4 treatment blocked the development of skin lesions and alopecia of the ears and face, and suppressed the thickening of the epidermis that accompanies leukocyte infiltration.

Use of Interleukin (IL)-34 to Treat Retinal Inflammation and Neurodegeneration

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.

Iodonium Analogs as Inhibitors of NADPH Oxidases and other Flavin Dehydrogenases and their Use for Treating Cancer

Diverse human cancers like colorectal, pancreatic, ovarian, melanoma, and pre-cancers express NADPH oxidases (NOX) at high levels. Reactive oxygen species (ROS) produced from metabolic reactions catalyzed by NOX in tumors are essential to the tumor’s growth. Though drugs that inhibit ROS production by NOX could be effective against a variety of human cancers, these types of drugs are not widely available.

Methods of Detecting Loss of Heterozygosity and Damaging Mutations in Immune-Related Genes Using Liquid Biopsies

Summary: 
The National Cancer Institute (NCI) seeks co-development partners and/or licensees for a liquid biopsy diagnostic assay capable of detecting loss of heterozygosity (LOH) and somatic mutations in genes important for antigen processing and presentation and interferon-γ response pathways.