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I understand that monoclonal antibodies are made by fusing a lymphocyte cell and a cancer cell but wouldn't this hybrid cell have double the normal number of chromosomes?
Question Date: 2003-11-01
Answer 1:

You're right that lymphocytes (B-cells) and cancer cells (myeloma cells) are used to make the "hybridomas" that produce monoclonal antibodies.

Your question is great because, as you may know, cells with abnormal chromosome numbers or abnormal amounts of DNA usually do not live.

Hybridomas, though, are probably somewhat of an exception to that rule. Almost all eukaryotic cells are diploid, which means they contain two copies of their genomes. It's not uncommon for cancer cells to have abnormal "ploidies," though. In fact, some cancers are defined by a specific chromosome being missing or by having too many copies of a chromosome (or part of one). Since polyploidy is fairly common in cancer cells and since cancerous myeloma cells are used to make the hybridomas, I think these hybridomas can survive being tetraploid (having four copies of the genome).

Also, it's important to remember that during the process of making the hybridomas, very few of the cells actually fuse and of those that do fuse, very few survive and divide. Ploidy problems could very well be one of the reasons why. My impression is that none of this matters to the biologists making the hybridomas, though. As long as they get one fused cell that reproduces and makes the monoclonal antibodies, they're happy; the fact that 99% of the other cells died is irrelevant. The one or few cells they get will divide pretty quickly into potentially huge colonies that make lots of the antibodies, and that's the goal.

So the short answer is that hybridomas probably are indeed tetraploid , or nearly so, and they survive anyway because cancerous cells can do that. An alternative (and less likely) answer is that hybridomas have some means of expelling excess DNA either directly or during the process of cell division. I'd place my money on the first answer, though. I hope that helps!


Answer 2:

You asked about monoclonal antibodies. You are correct about the chromosome number. The fusion cells, called hybridomas, have increased numbers of chromosomes.

Monoclonal antibody technology allows us to produce large amounts of pure antibodies in the following way:
We can obtain cells that produce antibodies naturally; we also have available a class of cells that can grow continually in cell culture. If we form a hybrid that combines the characteristic of "immortality" with the ability to produce the desired substance, we would have, in effect, a factory to produce antibodies that worked around the clock.

In monoclonal antibody technology, tumor cells that can replicate endlessly are fused with mammalian cells that produce an antibody. The result of this cell fusion is a "hybridoma," which will continually produce antibodies. These antibodies are called monoclonal because they come from only one type of cell, the hybridoma cell; antibodies produced by conventional methods, on the other hand, are derived from preparations containing many kinds of cells, and hence are called polyclonal. An example of how monoclonal antibodies are derived is described below.

A myeloma is a tumor of the bone marrow that can be adapted to grow permanently in cell culture. When myeloma cells were fused with antibody-producing mammalian spleen cells, it was found that the resulting hybrid cells, or hybridomas, produced large amounts of monoclonal antibody. This product of cell fusion combined the desired qualities of the two different types of cells: the ability to grow continually, and the ability to produce large amounts of pure antibody.

Because selected hybrid cells produce only one specific antibody, they are more pure than the polyclonal antibodies produced by conventional techniques. They are potentially more effective than conventional drugs in fighting disease, since drugs attack not only the foreign substance but the body's own cells as well, sometimes producing undesirable side effects such as nausea and allergic reactions. Monoclonal antibodies attack the target molecule and only the target molecule, with no or greatly diminished side effects.



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