Nat Med: A new breakthrough in immunotherapy! Human experimental data reveal the potential of CAR-NKT therapy to treat solid tumors.

Immunotherapy is one of the most promising development directions in the field of tumor therapy, among which CAR-T therapy is a unique flower.
, however, while the treatment has shown surprising efficacy in the treatment of blood tumors, it has suffered frequent setbacks in the treatment of solid tumors.
, a recent article in Nature Medicine offered new opportunities to enhance CAR-directed cancer immunotherapy, as well as new breakthroughs in solid tumor therapy.
The interim report, a phase 1 clinical trial conducted by researchers at Baylor College of Medicine and the University of North Carolina at Chapel Hill, suggests that genetically modified GD2-specific CAR (embedded antigens) that enable human NKT cell expression to specifically identify and attack neuroblastoma (NB) and leucocyte mesotonin-15 (IL-15), which supports the survival of NKT cells, may be important tools in the fight against cancer.
of the three NB patients who received the therapy, 1 received objective remission and the bone metastasis lesions subsided.
natural killer T-cells (NKT) are a special sub-group of T-cells with both T-cell-like and NK-cell-like surfaces.
previous studies have shown that NKT cells have a range of anti-tumor activity, and that the activation of these cells indirectly promotes anti-tumor responses mediated by NK and T cells.
, NKT cells have very little in the blood, and the way NKT cells fight tumors is mostly indirect.
then, the researchers used CAR to "arm" patients' NKT cells, allowing them to attack tumors directly, while "equipping" lecytokine-15 (IL-15) to improve the viability of these cells.
treatment, the purity of NKT cells in all 3 patients was more than 90%.
the researchers cultured the cells in vitro for 15 days (patient 1), 14 days (patient 2) and 9 days (patient 3), and then infused them back into the patient.
results showed good CAR-NKT cell tolerance in all patients.
the patient's weekly blood NKT cell amplification frequency and absolute quantity were higher than the baseline level during the 4-week evaluation period.
the dilation and continuity of CAR-NKT cells in patients, however, the time it takes for cells to grow in vitro may affect the in vivo amplification efficiency of CAR-NKT cells.
infusion of the corresponding cell products, patient 3 had the highest absolute number of CAR-NKT cells, while patient 1 had the lowest absolute number of CAR-NKT cells.
, the researchers conducted a series of tumor-stimulating trials that added NB cells to car-NKT cells in three patients every five days, five times.
After adding three NB cells, patient 1's CAR-NKT cells gradually lost cytotoxic activity, while patients 2 and patient 3's CAR-NKT cells remained capable of killing NB cells and a stronger proliferation response throughout the period.
further experiments, the researchers found that CAR-IL15 NKT cells could be detected in the patient's exodus, which amplified after infusion and transferred to bone metastases and bone marrow, acting as anti-tumor activity and inducing the tumor to subside.
in 3 patients, at least 50% of bone metastasis lesions were eliminated.
Leonid S. Metelitsa, a pediatric oncologist at Baylor College of Medicine and Texas Children's Cancer Center, said: "Clinical trials have shown that it is possible to enhance the anti-tumor capacity of immune cells with natural anti-tumor properties by designing synthetic subjects, which offers new hope for using this strategy against hard-to-treat solid tumors.
, this study shows that CAR-NKT cells can be extended to clinical scale and can be safely used to treat cancer patients.
, researchers have licensed the NKT platform developed to Kuur Therapeutics to advance clinical applications.
.