Science Advances: Delivering CAR-T cells via hydrogels to improve the treatment of solid tumors

In recent years, the rise of tumor immunotherapy has brought new hope to the majority of cancer patients .

Since 2017, a total of 7 CAR-T therapies have been approved for marketing in the world, and two CAR-T therapies have also been listed in China.

On April 8, 2022, researchers from Stanford University published a research paper titled: Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors in the journal Science Advances .

The study develops a simple and efficient method of CAR-T delivery: CAR-T cells and cytokines are added to a specially formulated hydrogel, which provides a temporary, immune cell-activating environment, and then pump activated CAR-T cells to attack the tumor tissue

More importantly, this delivery method has the potential to treat distant tumors, which opens new doors for CAR-T therapy in solid tumors

"A lot of CAR-T research focuses on how to make better cells, but very little research focuses on how to make CAR-T cells work more efficiently in the body," said Eric Appel, Ph.

At present, intravenous injection is the main way of CAR-T cell therapy

To use an image metaphor, blood cancer is like an isolated and helpless straggler, so it is easier to be defeated, but solid tumors are like troops hiding in a city, obviously more "deep-rooted", and CAR-T cells are very Difficult to penetrate into solid tumors to attack cancer cells

Diagram showing the difference between "hydrogel therapy" (right) and conventional intravenous injection (left)

To potently activate CAR-T cells, the cells must be exposed to high concentrations of specialized signaling proteins, called cytokines, for prolonged periods of time, which prompt the engineered immune cells to rapidly replicate and prepare to destroy tumors

So, to overcome this difficulty, the research team created a special hydrogel that attaches around tumor tissue and can temporarily house cytokines and CAR-T cells, where immune cells grow and proliferate, and then continuously "pump" out" CAR-T cells kill cancer cells

Schematic diagram of the preparation of the hydrogel

The hydrogel consists of water and two components: a polymer made from cellulose found in plants, and biodegradable nanoparticles

Dr Abigail Grosskopf, first author of the study, said: "The material can be injected through a small needle, but after injection, the 'velcro' takes effect and transforms into a strong gel structure

After identifying the optimal hydrogel formulation to deliver cancer treatment, the research team applied its approach to mice with tumors

Not only that, but the research team also tried injecting the hydrogel farther away from the tumor to see if the therapy could treat distant tumors

Hydrogel is effective in treating distal subcutaneous medulloblastoma in mice

Corresponding author Dr.

As for safety, the hydrogel caused no adverse inflammatory response in mice and was completely degraded in the body within a few weeks

Hydrogels can prolong retention of stimulating cytokines and exhibit controlled degradation in vivo

Overall, the study developed a simple and efficient method of CAR-T cell delivery by encapsulating CAR-T cells and cytokines through a specially formulated hydrogel that is continuously "pumped" at the site of solid tumors Activated CAR-T cells rapidly cleared tumors
.

More importantly, this delivery method has the potential to treat distant tumors, which opens a new door for CAR-T treatment of solid tumors and points out a new direction for humans to completely conquer cancer
.
In addition, the hydrogel delivery method has the advantage of being simple to prepare, which helps to simplify the process and reduce the cost and price of CAR-T therapy
.

Original source:

ABIGAIL K.
GROSSKOPF, et al.
Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors .
SCIENCE ADVANCES, 8 Apr 2022, Vol 8, Issue 14? DOI: 10.
1126/sciadv.
abn8264.