NASA’s cell culture experiment tests Azonafide Antibody-Drug conjugates

t helper cell antibody-antigen reaction

Researchers from NASA have undertaken a new experiment to test the efficiency of Azonafide antibody-drug conjugates in the microgravity environment of International Space Station. There has been a various research conducted in the earth under laboratory condition to check the efficiency of cancer cell killing drug but those experiments raise a lot of question because of the cell culture method used by most of the experiments.

NASA is on mission to conduct various Genes in Space experiment.

Laboratory condition of cell growth in earth shows two-dimensional growth in which cells are scattered in the culture media which will not mimic the nature of targeted cell growth in the human body. The finding from the above cell culture will not give the clear picture of the biochemical action of the drug inside human body hence NASA scientist are testing the efficiency of the drug in International Space Station’s unique microgravity environment where the three-dimensional growth of cell culture has been reported.

The Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates (ADCs) in Microgravity investigation seeks to activate immunogenic cell death within the cancer cells, which should kill cancer and prevent the disease from reoccurring in the future. The experiment explores a new drug and antibody combination that may increase the effectiveness of the treatment and decrease secondary side effects associated with chemotherapy.

Cytotoxic drugs act by directly killing selected cells, affecting both the growth and behavior of remaining cells to treat unwanted malignancies and tumors.  Cytotoxins can be used to treat various ailments including rheumatoid arthritis, and systemic lupus erythematosus. They are commonly used in oncology therapeutics, which represent one of the fastest-growing segments of the pharmaceutical and biotechnology industry.

Current chemotherapy drug doesn’t work by differentiating between healthy cells and cancer forming an abnormal cell which sometimes may kill the healthy cells. Azonafide Antibody-Drug Conjugates (ADCs) has an advantage over traditional chemotherapy treatment in which it is designed specifically to kill only cancer cell without affecting the healthy cells.

What is Azonafides?

Chemical Structure of Azonafide
Chemical Structure of Azonafide derivative

Azonafide is a chemical compound which when released into a human body acts as a cytotoxic product by killing the cell. In the pharmaceutical industry, Azonafide derivatives are used as potential anti-tumor agents which have shown enhanced activity against various cancer models, especially leukemia’s, breast cancer and melanoma.

Azonafides are a class of DNA intercalators with the ability to conjugate to an antibody via an amide linkage.  Potency has been validated across all NCI-60 cell lines including colorectal, lung, breast, renal, and other solid and blood cancers. They have unique ability to both induce cancer cell death and activate the immune system through immunogenic cell death (ICD).  These pathways have shown unique efficacy in treating drug-resistant tumors and cancer stem cells.

Azonafide ADC’s carry an Azonafide cytotoxin attached to an antibody specific to tumor cells and not healthy cells, thereby avoiding many of the side effects associated with traditional forms of chemotherapy.

Significance of the experiment:

  • Efficacy and Metabolism of Azonafide Antibody-Drug Conjugates in Microgravity evaluates the molecular interactions and efficacy of Azonafide ADCs in cancer cells under conditions of microgravity.
  • This study will support drug metabolism studies that will compare the concentration of Azonafide toxic payload within cancer cells to the concentration of Azonafides in non-cancer cells to determine multiplier effect of ADC targeting.
  • These drug metabolism and efficacy studies give insight into how Azonafide antibody-drug conjugates behave in the human body.
  • Knowing how drug combinations work in microgravity is increasingly important to treat astronauts with diseases such as cancer during the deep-space missions.

Structure and mechanism of action :

The Azonafide antibody-drug conjugates (ADCs) is a combination of two molecules: a cancer-killing Azonafide drug and an antibody, which may enable a targeted approach for cancer treatment by only allowing the drug to kill cancer cells, while leaving the healthy cells intact. The antibody acts like a connector block, in which on one side of it will only bind to the drug and the other side will only bind to cancer cells and not healthy cells. So by combining these two, the idea is to decrease the nasty side effects of chemotherapy.

Azonafides are conjugated directly to tumor-targeting moieties called antibodies to deliver this immune-activating payload directly to the tumor. Once the Azonafide Antibody-Drug Conjugates binds to the tumor surface, the construct is internalized by the tumor cells where the Azonafide is released and can initiate cell death.

Azonafide antibody-drug conjugates enable local delivery of the drug to the tumor site, thereby avoiding the toxic side effects associated with systemic chemotherapy. In addition, Azonafides activate immunogenic cell death, which initiates an anti-tumor immune response that should produce immunological memory to prevent disease recurrence.

A team of researchers from Oncolinx will test the efficacy and drug metabolism of Azonafide antibody-drug conjugates in microgravity cultures and, as such, accelerate the timeline to translational applications of the research. This company has been given exclusive access to these Azonafide antibody-drug conjugate from National Cancer Institute (NCI) along with funding for related studies.

 

The efficacy and metabolism of Azonafide Antibody-Drug Conjugates in Microgravity experiment is integrated by BioServe Space Technologies at the University of Colorado, Boulder. The experiment is hosted in four MultiWell BioCells and two BioCell Habitats and makes use of BioServe’s Space Automated Bioproduct Lab (SABL) and Atmosphere Control Module (ACM) to culture carcinoma (lung cells, Calu-3) at 37°C and 5% carbon dioxide (CO2).

Oncolinx a Pharmaceutical company works with several academic groups and startups with respect to protein/aptamer-drug conjugates and immunotherapy combination studies. It is engaged in shared-data Material-Transfer Agreement (MTA) with other partners where Oncolinx can conjugate the Azonafide via patented linker technology to antibody and build a testable ADC

Although this combination may decrease many of the negative side effects of chemotherapy, it may also have its own side effects, though potentially less severe and short-lived.

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