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I somewhat understand that some monoclonal antibodies are developed from the cells of mice, or a fusion of human and mice genes.

When something is a fully human monoclonal antibody does that mean it came from some person? What type of human cell did it come from? Will the drug always be from that original human?

I read that they're derived from something called a phage display technique. I'm guessing this is another type of way to fuse genes together, but with all human cells.

Where do the cells come from?

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I found this small article that seems to cover all your questions:

https://www.sciencedirect.com/topics/medicine-and-dentistry/human-monoclonal-antibody

Summary:

Being considered a human monoclonal (many of the identical antibody, as opposed to different antibodies for the same target) antibody does not mean it is produced by a human body; it means that the fc-region of the antibody is human-like, which aims at avoiding immune reactions against that antibody if injected into humans. So the human antibody can originate from animals (e.g. rats or rabbits) with humanized antibody genes or from immortalized human cell-lines (lymphocytes).

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  • $\begingroup$ Thank you. I was able to access the full article, and was surprised to see it's from 1998. It has some sections on general approaches to making monoclonal antibodies and human monoclonal antibodies. The 1998 article explains that for ethical reasons it's not possible to "hyperimmunize humans and typically the only source of B lymphocytes is peripherial blood ... less suitable for fusion." It then goes on to discuss workarounds. The only human work around is to "immortalize" the B lymphocytes with the Epstein-Barr virus. $\endgroup$
    – Louis Waweru
    Oct 31, 2019 at 15:24
  • $\begingroup$ The link you shared has newer information, and talks about using "bacteriophage display library of human variable region sequences and selects for antigen binding in vitro. The selected genes are then combined with human constant region genes to reconstitute a complete IgG antibody." This sounds like the current state of the art. Doesn't sound fully human either! $\endgroup$
    – Louis Waweru
    Oct 31, 2019 at 15:25
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    $\begingroup$ Link-only answers are generally not acceptable on Stack Exchange sites. The link may change or become unreachable in the future, and without a summary of what the link contains this answer would be useless. Please summarize what is in the link (don't just copy and paste) and use the link solely for reference. If you remove the link and the answer cannot stand on its own, it is not a good answer. $\endgroup$
    – Bryan Krause ♦
    Oct 31, 2019 at 16:25
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    $\begingroup$ Sorry, I didn't know that and obviously just tried to help. $\endgroup$
    – KaPy3141
    Oct 31, 2019 at 16:46
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    $\begingroup$ @KaPy3141 That's fine - my comment is one of the standard ones and is intended to help you know so you can improve your answer, since you can edit it to fix the problems. Welcome to Biology.SE! $\endgroup$
    – Bryan Krause ♦
    Oct 31, 2019 at 18:51
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Following technquies are used for developing fully human monoclonal antibodies:

  • Complementarity-determining region (CDR) engraftment: This method is performed by preparing cDNA library. CDRs are amplified from a mouse hybridoma cell line, and later these sequences are engineered into the human variable light and heavy chains.

  • Using transgenic mice with human Immunoglobulin genes: Hybridoma fusion technique is used to synthesize human monoclonal antibody. The transgenic mice expresses DNA encoding human immunoglobulin genes.

  • Display technologies using phage, yeast, and ribosome: Heavy and light chain cDNA from human B-cells is used to construct a library. Various heavy and light chain pairs are expressed on the phage. These phage are screened for antigen binding. Further this recombinant monoclonal antibody is synthesized using prokaryotic, yeast expression system, insect or mammalian cell expression system.

Display technique uses the principle of specific antibody production but employ micro-organisms in case of phage display and cell free extracts in case of ribosome display. These systems depend on creation of gene libraries constructed using peripheral blood from humans. The products synthesized in this procedure are antibody fragments of Antigen binding (Fab) or Single-chain variable (scFvs), having complete human sequence.

Via: http://www.pharmtech.com/novel-process-developing-fully-human-monoclonal-antibodies?id=&sk=&date=&pageID=3

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  • $\begingroup$ Took a while to do some additional reading, but thank you. I think I better understand. Would you mind letting me know if you don't fully understand this though? $\endgroup$
    – Louis Waweru
    Apr 25, 2021 at 5:48
  • $\begingroup$ Also, Link seems dead. $\endgroup$
    – Louis Waweru
    Apr 25, 2021 at 5:54

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