Fusion protein derived from algae to treat cancer would offer financial relief to patients
Chlamydomonas reinhardtii known as green algae has been developed into a fusion protein that is a carbon copy of one that is under development by pharmaceutical companies but would carry a proposed cost of $100,000 however, this new anti-cancer biotech drug could be reduced down to $50,000 allowing a reduction of 90% in manufacturing costs which would provide financial relief to patients.
Stephen Mayfield, Director, San Diego Center for Algae Biotechnology and John Dove Isaacs Chair of Natural Philosophy Professor, Section of Molecular Biology, UC San Diego stated “Because we can make the exact same drug in algae, we have the opportunity to drive down the price down dramatically.”
Mayfield and fellow researchers in the Mayfield Lab had shown that they could develop an anti-cancer biotech drug that is a carbon copy of the one under development by a biotech company. This derived algae drug has been tested on mice and demonstrated to have the same cancer effect.
The researchers manipulated the algae to develop a protein that combined part of an antibody targeting CD22, a molecule belonging to the SIGLEC family of lectins (sugar-binding proteins) to zero in and bind the cancer cells and the exotoxin A produced by Pseudomonas aeruginos (a common bacterium that can cause disease in animals and humans) which then destroys the bound cells, known as fusion protein.. Fusion proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. These proteins are currently are produced by pharmaceutical companies in a complicated two-step process. Step one developing the antibody domain in a Chinese hamster, or CHO, cell (Chinese hamster ovary cells) which are widely used mammalian cells for transfection, expression, and large-scale recombinant protein production. Afterwards the antibody is purified then chemically attached to a toxin outside the cell. Then the final protein is re-purified.
“We have a two-fold advantage over that process.” “First, we make this as a single protein with the antibody and toxin domains fused together in a single gene, so we only have to purify it one time. And second, because we make this in algae rather than CHO cells, we get an enormous cost advantage on the production of the protein,” said Mayfield according to UCSD News Center.
According to Mayfield this type of fusion protein could not have been made in a mammalian CHO cell, due to the fact the toxin would have the fusion protein. He further notes that because the protein was produced in algae’s chloroplasts (the part of algal and plant cells where photosynthesis takes place) the algae was not killed. The protein was isolated inside the chloroplasts.
“And the chloroplast has different proteins from the rest of the cell, and these are not affected by the toxin. If the protein we made were to leak out of the chloroplast, it would have killed the cell. So it’s amazing to think that not one molecule leaked out of the chloroplasts. There are literally thousands of copies of that protein inside the chloroplasts and not one of them leaked out,” said Mayfield.
According to Mayfield developing this particular fusion protein was reasonably direct because two fusion domains were involved; one to recognize and bind the cancer cells and the other one to kill the cells. Mayfield believes this same method may be used to engineer algae to develop more complex proteins that have multiple domains.
Mayfield comments “Can we string together four or five domains and produce a designer protein in algae with multiple functions that doesn’t exist in nature? I think we can?”
In closing he adds “at some point you can start thinking about medicine the same way we think about assembling a computer, combining different modules with specific purposes. We can produce a protein that has one domain that targets the kind of cell you want to impact, and another domain that specifies what you want the cell to do.”
David Hansen, Chief Executive Officer and President of MabVax Therapeutics Inc., related to UT San Diego, the algae method of manufacturing is of interest providing it works. MabVax is developing antibody based vaccines.
The achievement of the researchers from Mayfield Lab is detailed in a paper in this week’s early online issue of The Proceedings of the National Academy of Sciences.
In May, researchers from the Mayfield Lab used algae to produce malaria proteins that elicited antibodies against Plasmodium falciparum in laboratory mice and prevented malaria transmission.
The research team succeeded in engineering algae to develop possible candidates for a vaccine that would prevent transmission of the parasite that causes malaria. This achievement could lead the way for development of an inexpensive way to protect billions of people from the mosquito-borne disease caused by a parasite.
According to the CDC in 2010, an estimated 216 million cases of malaria had occurred worldwide and 655,000 people died, with 91% being in the African region.
This study appeared in PLOS ONE, published May 16, 2012.
Research from Stephen Mayfield and research team can be viewed online at the Mayfield Lab website.