Improving the Infrastructure for Therapeutic Transfer of T Cells

I suspect that we'll see spreading use of immune cell transfer therapies in the years ahead. The time is right for it: stem cell researchers are continually improving their ability to generate cells to order, knowledge of how the immune system works in detail is growing, and so is the understanding of just how important immune system decline is in aging. Somewhere between today and a future in which an age-damaged immune system can be completely restored to youthful function lies a span of decades in which regular infusions of tailored immune cells are a routine part of older life, a treatment that temporarily enhances immune system function across the board, or which can be used to attack specific targets such as an infection or a cancer.

For this to come to pass the infrastructure for such therapies must improve, becoming more efficient, more reliable, and much less costly than is presently the case. This is happening now, step by step, such the progress cited in this article. It is aimed at use for transplant patients, but should be relevant to a range of similar future applications:

Therapeutic transfer of virus-specific T cells to immunocompromised patients can help battle life-threatening infections, but the process for generating such cells is lengthy and laborious. A [recently published] paper suggests a speedy alternative. Ten days in culture was all it took for researchers to generate multivirus-specific T cells that, when transferred into transplant patients, could wipe out multiple infections at once. "The original manufacturing processes were really convoluted and complicated." They involved using live viruses to infect donor B cells, and then using those cells to stimulate T cells. "With all that, we are talking 10 to 12 weeks of manufacturing." Furthermore, the live viruses in question are considered biohazards. When a procedure is that difficult and hazardous, "it's never going to go beyond specialized academic centers."

[The researchers] streamlined the process, bypassing the live virus and B cell steps, and instead stimulating the T cells directly with peptides. A similar technique has been used previously to generate T cells specific for fighting cytomegalovirus. But the new method extends the concept, using a mix of peptides that together cover the antigenic proteins of five of the most common viruses to infect transplant patients.

When active T cell preparations were transferred into bone marrow transplant patients suffering viral infections the cells led, in almost all cases, to resolution of the infections. In eight patients treated, 15 of 18 total infections among the individuals were resolved, while one was reduced. Three additional patients were given the T cells prophylactically and remained infection-free for more than three months. The varying ability of the T cell preparations to tackle multiple viruses is thought to be due to the donor's prior exposure to the viruses in question. That is, if the donor has not tackled the virus before then, their blood would lack the necessary memory T cells. A future goal would be "generating such antigen-specific T cells from naive cells as opposed to people who have already got a T cell memory to the antigens."

Link: http://www.the-scientist.com/?articles.view/articleNo/40353/title/Speeding-Up-Antiviral-T-Cell-Production/

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