Using Donor Immune Cells To Mass-Produce CAR-T Autoimmune Therapies

As exciting as immunotherapies are in terms of fighting cancer, correcting autoimmune disorders and so on, they come with a major disadvantage. Due to the current procedure involving the use of a patient’s own immune (T) cells, this making such therapies rather expensive and involved for the patient. Recent research has therefore focused on answering the question whether T cells from healthy donors could be somehow used instead, with promising results from a recent study on three human patients, as reported in Nature.

The full study results (paywalled) by [Xiaobing Wang] et al. are published in Cell, with the clinical trial details available on the ClinicalTrials.gov website. For this particular trial the goal was to attempt to cure the autoimmune conditions of the three study participants (being necrotizing myopathy (IMNM) and diffuse cutaneous systemic sclerosis (dcSSc)). The T cells used in the study were obtained from a healthy 21-year old woman, and modified with chimeric antigen receptors targeting B (memory) cells. Using CRISPR-Cas9 the T cells were then further modified to prevent the donor cells from attacking the patient’s cells and vice versa.

After injection, the CAR-T cells got to work, multiplying and seeking out the target B cells, including the pathogenic ones underlying the autoimmune conditions. This persisted for a few weeks until the CAR-T cells effectively vanished and new B cells began to emerge, with a clear decrease in autoantibodies. Two months after beginning treatment, all three participants noted marked improvements in their conditions, which persisted at 6 months. For the woman with IMNM, muscle strength had increased dramatically with undetectable autoantibody levels, and the two men with dcSSc saw scar tissue formation reversed and their skin condition improve massively.

It remains to be seen whether this period of remission in these patients is permanent, and whether there any side effects of CAR-T cell therapy. We previously reported on CAR-T cell therapies and the many promises which they hold. Depending on the outcome of these early trials, it could mean that autoimmune conditions, allergies and cancer will soon be worries of the past, marking another massive medical milestone not unlike the invention of vaccines and the discovery of antibiotics.

CAR T Cell Immunotherapy And The Quiet Hope For A Universal Cancer Treatment

All of us have to deal with the looming threat of developing cancer during our lifetime, no matter how good our genetics are, or how healthy our lifestyle is. Despite major improvements to the way that we treat and even cure cases of cancer, the reality today is that not all types of cancer are treatable, in many cases there’s the likelihood that one day it will return even after full remission, and chemotherapy in particular comes with potential life-long health issues. Of the most promising new and upcoming treatments, immunotherapy, is decidedly among the most interesting.

With this approach, it is the body’s own immune system that is taught to attack those cancer cells, requiring little more than a few tweaks to T-cells harvested from the patient’s body, after which they’re sent on their merry cancer-killing way.  Yet as simple as this sounds, finding the right characteristics which identify the cancerous cells, and getting a solid and long-lasting immune response is a tough challenge. Despite highly promising results with immunotherapy treatment for non-solid cancers like leukemia – that have resulted in almost miraculous cures – translating this success to other cancer types has so far remained elusive.

New research now shows that changing some characteristics of these modified (chimeric antigen receptors, or CAR) T-cells may be key to making them significantly more long-lived and effective within a patient’s body. Is this the key to making immunotherapy possible for many more cancers?

Continue reading “CAR T Cell Immunotherapy And The Quiet Hope For A Universal Cancer Treatment”

CRISPR Could Fry All Cancer Using Newly Found T-Cell

One of the human body’s greatest features is its natural antivirus protection. If your immune system is working normally, it produces legions of T-cells that go around looking for abnormalities like cancer cells just to gang up and destroy them. They do this by grabbing on to little protein fragments called antigens that live on the surface of the bad cells and tattle on their whereabouts to the immune system. Once the T-cells have a stranglehold on these antigens, they can release toxins that destroy the bad cell, while minimizing collateral damage to healthy cells.

CAR T-cell therapy process via National Cancer Institute

This rather neat human trick doesn’t always work, however. Cancer cells sometimes mask themselves as healthy cells, or they otherwise thwart T-cell attacks by growing so many antigens on their surface that the T-cells have no place to grab onto.

Medical science has come up with a fairly new method of outfoxing these crafty cancer cells called CAR T-cell therapy. Basically, they withdraw blood from the patient, extract the T-cells, and replace the blood. The T-cells are sent off to a CRISPR lab, where they get injected with a modified, inactive virus that introduces a new gene which causes the T-cells to sprout a little hook on their surface.

This hook, which they’ve dubbed the chimeric antigen receptor (CAR), allows the T-cell to chemically see through the cancer cells’ various disguises and attack them. The lab multiplies these super soldiers and sends them back to the treatment facility, where they are injected into the patient’s front lines.

Continue reading “CRISPR Could Fry All Cancer Using Newly Found T-Cell”