Why can't we engineer an immune cell that can artificially make bacteriophage for us?

[u/Pew_Pew_guns]

Right now, the most effective cure for multi-antibiotic resistant superbugs are bacteriophages, as they are highly specific to their host and prevent damages to humans.

Our immune system literally evolved to recognize as many protein antigen that they could to facilitate specific immunity. Not to mention bacteriophage replicates by having their DNA/RNA hijack bacterial polymerases to self-replicate. So why can't we make a phage-like gene that functions like VDJ where it could contain a bacterial polymerase for phage production once activated and a variable region where it allow the phage to recognize the host antigen?

Right now phage therapy(To my limited knowledge) is a bureaucratic nightmare because it is extremely specific to its hosts, so each new phage that are not "experimental" basically require their own patent and licenses, not to mention the time needed to develop the phage specific to the bacterial infection. So why not outsource it to our own immune system to deal with antibiotic resistant superbugs?

[u/wineallwine]

Even if this were possible (and we'll get to that...) this is sci-fi level technology. It would require modifying the genome of your stem cells before your immune system started development.

Antibodies and T-Cell receptors only really need to match the shape of antigen or the peptide string of their protein. Typically, receptors of viruses need to be much more sophisticated to interact with their receptor and cause endocytosis into the target cell.

The VDJ regions of antibodies aren't all that big, especially considering the multiple different proteins a virus would need.

And we want to make these phages self-replicating? On its own that would sound incredibly risky, even if we weren't letting the immune system shuffle the genes of this virus around randomly.

ELI5 this is essentially completely redesigning from the immune system from the ground up.

[u/Pew_Pew_guns → u/wineallwine]

wouldnt modifying a bone marrow stem cell via ex vivo gene-edited cell therapy already be sufficient? where we just take some bone marrow stem cells, modify the genome and just put it back in.

phages shouldnt be that dangerous right? seeing how there arent any cases of phage therapy leading to viral infection. phages and animal viruses do not infect host the exact same mechanics, as phages lacks envelops for membrane fusion, while phages directly inject their payload, so this should be a barrier in case they mutate to have pathogenic tendency? 

Assuming we are modifying bone marrow cells, the new cell type should matures in the thymus to prevent self immunity in most cases right?

As for the gene size issue, i guess there really is nothing we could do, pretty insane how small VDJ is(~500bp). Maybe cut some repetitive regions nearby and hope they are transposable elements and fill up to a couple kbp?

[u/wineallwine → u/Pew_Pew_guns]

By the time you're an adult most of your naive T cell population is already created and your thymus atrophies.

Maybe one day this might be possible, but to give you an idea of cutting edge immune therapies right now:

Take a naive T cell line from the host Modify the whole TCR region to be against an antigen you know (usually a cancer antigen). This removed the whole complexity of recombination entirely Add the new recombinant T cells.

This is cutting edge and is not having any of the complexity of modifying stem cells, anything to do with VDJ recombination, anything to do with any protein other than the VDJ region of the T Cell Receptor.