Software for Modeling Delivery and Penetration of Antibody Conjugates

The National Cancer Institute (NCI) seeks parties to license software for modeling the targeted delivery of anti-cancer agents in solid tumors.

The software models the permeability and concentration of intravenously administered antibody anti-cancer agent conjugates in solid tumors.  The models can be used to determine optimal dosing regimen of a therapeutic in a particular cancer type.  Thirty factors that affect delivery rates and efficiencies are analyzed as variables in generating the models.

Sensitizing Cancer Cells to DNA Targeted Therapies

Chk2 is a protein kinase activated in response to DNA double strand breaks. In normal tissues, Chk2 phosphorylates and thereby activates substrates that induce programmed cell death, or apoptosis, via interactions with p53, E2F1, PML proteins. In cancer tissues, where apoptosis is suppressed, Chk2 phosphorylates and inactivates cell cycle checkpoints (via interactions with Cdc25, phosphatases and Brca1 proteins), which allows cancer cells to repair and tolerate DNA damage.

Neoantigen T Cell Therapy with Neoantigen Vaccination as a Combination Immunotherapy Against Cancer

Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes autologous, antitumor T cells to attack tumors through recognition of tumor-specific mutations, or neoantigens. A major hurdle in the development of ACT is the exhausted phenotype exhibited by many neoantigen-specific T cells, which limits their efficacy and prevents a sustained immune response. 

Antisense Oligonucleotides against Cancer Cell Migration and Invasion

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.

HIV-1 Therapeutic Inhibits Viral Entry

Soluble forms (sCD4) of human CD4, the HIV-1 primary receptor, are potent HIV-1 entry inhibitors. Both four-domain (D1-4) and two-domain (D1D2) sCD4 and their fusion proteins have been tested as candidate therapeutics in animal models and in human clinical trials and were well tolerated by patients with no significant clinical or immunologic toxicities and exhibited significant inhibitory activities. However, their activities were transient and the virus rapidly rebound.

Method for Targeted Therapeutic Delivery of Proteins into Cells

Current methods to deliver proteins into cells (e.g., using retrovirus, DNA transfection, protein transduction, microinjection, complexing the protein with lipids, etc.) have many shortcomings, such as lack of target specificity toxicity, or unwanted random integration into the host chromosome.  Protein transduction is an emerging technology for delivering proteins into cells by exploiting the ability of certain proteins to penetrate the cell membrane.  However, the majority of the proteins delivered by this means are usually trapped and subsequently degraded in the endosomes-lyso

High-throughput Assay to Identify New Cancer Drugs

 The National Cancer Institute seeks parties interested in collaborative research to evaluate or commercialize a diagnostic tool that can identify new drugs that increase chromosome instability.  Although chromosomal instability is generally thought of as a driver of tumor growth, a threshold level exists where CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically.

Gene Signature for Predicting Solid Tumors Patient Prognosis

HCC is the most frequent malignant tumor in the liver and the third leading cause of cancer death worldwide.  A progressive sequence of somatic mutations and epigenetic changes of oncogenes or tumor suppressor genes are believed to cause tumor development. However, high genomic instability in tumors causes the accumulation of genomic aberrations that do not contribute to tumor progression. Therefore, it is important to distinguish between ''driver'' mutations that are functionally important and ''passenger'' mutations that do not provide a selective advantage to the tumor cells.