Antibody Intracellular Delivery Technology
Without an appropriate transport mechanism, the antibodies are unable to cross the plasma membrane of living cells and reach their intracellular targets.
The formulation and properties of the BioCellChallenge technology help to deliver the antibodies directly into the cytosol of living cells, with no specific prior preparation and without the need for chemical modification of the antibodies. Antibody activity is not affected in any way.
ImmunoCellin Test in vitro
Antibodies are integrated within lipidic structures through hydrophobic and electrostatic interactions. No chemical coupling occurs guaranteeing that the antibody is not denatured and maintain its full activity. The antibody-lipid complexes are then able to interact with the cell membrane. A process of “fusion-membrane rearrangement” occurs, allowing the antibody to be delivered directly inside the cytosol.
0.25 µg of a DyLight labeled Mouse non-specific antibody has been delivered into Human NIH3T3 cells in a 96-well plate with 0.5 µL of ImmunoCellin reagent.
Result: The antibody localizes non specifically into the cytosol
Anti-Nucleoporin p62 antibody
0.25 µg of a FITC Mouse Anti-Nucleoporin p62 antibody (BD Transduction Laboratories) has been delivered into Human Lung cells in a 96-well plate with 0.5 µL of ImmunoCellin reagent.
Result: The antibody accumulates onto the nuclear envelope
ImmunoCellin Test in vivo
The tests were conducted in 18 animal models, from January through July 2015. They showed that the intracellular delivery of a specific monoclonal antibody directed against the Ras oncoprotein, which is implicated in many cancers, significantly reduces the proliferation of tumor cells.In all cases, the animals’ lives were prolonged by up to 30%. Recovery was observed in 33% of cases. No toxicity-related mortality or inflammation was observed, or any abnormal change in the growth of the animal.
New fields of investigation
Antibodies are not able to pass through plasmic membranes of live cells towards potential intracellular targets. Thousands of antibodies have been developped as tools for the scientists. Their intracellular delivery opens new fields of investigation for both research and therapeutic applications.
This system is very well adapated to modulate intracellular protein functions. For example, siRNA intracellular delivery allows to shut down the expression and all the functions of the targeted protein. However, if this protein has several different function inside cells, it is more advisable to inhibit only one of them by using a specific monoclonal antibody.