CAR T-cell therapy has captured the attention of major pharmaceutical companies with a continuing influx of positive results. CAR T (chimeric antigen receptor) therapy has improved survival rates for pediatric patients diagnosed with relapsed and recurring leukemia.
Hematology.org carried an article saying that by definition, a patient’s immune cells are modified to kill cancer cells. Conversely, solid tumors have a limited number of cytokines and can send out anti-immune signals to turn off CAR T cells. The result is a treatment that is less effective.
And yet the CAR T cell therapy has seen continuous expansion. Attendees at this year’s annual ACR meeting were presented with current information about the program.
Cytokines (small proteins) assist in controlling the body’s response to infection and disease. The cytokine pathways can be activated by several factors, one of which is injecting cytokines into the tumor. However, the scientists found that toxicity continued to have a negative effect on these strategies.
Modular Cytokine Receptors
A new system was created by scientists at the St. Jude Hospital for Children that improves the efficacy and safety of immunotherapy for solid tumors.
Dr. Mathew Bell, a first author, explained that the team of scientists designed a modular chimeric antigen receptor that was added to CAR T cells resulting in increased efficacy in solid tumor models. Cytokines (small proteins) assist in controlling the body’s response to infection and disease.
By using the new St. Jude system, scientists can deliver the pro-immune signals directly to the CAR T cells and eliminate toxicity.
Dr. Bell further explained that the technology carries the potential to improve T-cell therapy in brain tumors and solid tumors.
CAR-T and Systemic Lupus
A research team at Novartis Pharmaceuticals reports that its CAR-T product which was initially developed to treat CLL has been effective in treating three patients diagnosed with systemic lupus erythematosus (SLE).
CAR-T technology was used to deplete B cells that produced autoantibodies. The team found that harmful B cells will not return after reconstitution.
CAR-T and the Nuremberg Germany Team
Dr. Georg Schett and his team of scientists at the Erlangen-Nuremberg University in Germany are well known for their efforts in studying the new technology
The team reported curing one lupus patient and the following year an additional five lupus patients were reported as being cured.
Recently a total of 15 patients had a single dose of treatment and a six month follow-up. The various diagnoses were:
- systemic lupus erythematosus
- systemic sclerosis
- idiopathic (of unknown cause) inflammatory myopathies
With the exception of one lupus patient the remaining patients reported nearly complete or entirely complete removal of all six major autoantibody species.
The main point of the study pertained to a patient’s reaction to standard vaccines, including COVID-19, and whether they had retained an immunity to infections after being vaccinated.
Of the fifteen patients, five patients received vaccines following their CAR-T treatment. All five people exhibited a fairly normal antibody response when they were tested at a later date.
Currently, scientists are focused on keeping CAR-T cells functional for a longer period. Dr. Shivani Srivastava, a Fred Hutchinson Research Center immunologist, explained that using a CAR or T cell continuously causes it to lose its efficacy.
Dr. Crystal Mackall at Stanford University engineered a CAR-T cell that can be used intermittently thereby improving the T cell’s function.
Most tactics, however, have not been successful in eradicating the cancer and preventing it from returning. According to Dr. Macrall, “This may be a lifelong project.”
