Mesothelioma
Most car-t cell therapies need to target cancer cell related membrane proteins, while Shanghai Cell Therapy Group uses a new method to not only target cancer cell related membrane proteins, but also secrete antibodies to change the microenvironment around tumors. This method is derived from the “nano antibodies” naturally produced by alpacas and camels. The “nano antibodies” in alpacas help car-t cells treat solid tumors.
A total of 10 patients with advanced relapsed / refractory mesothelioma were included in this clinical trial. All patients received at least 2 lines of chemotherapy and failed. Seven patients received 1 to 2 times of apd1-mescar-t cell reinfusion, with the reinfusion dose ranging from 1 × 106~1.5 × 107car-t / kg, 6 patients completed the safety and preliminary efficacy evaluation after reinfusion. On 28 days after reinfusion, the patient received enhanced CT or PET-CT to evaluate the initial efficacy of the product.
Of the 6 evaluable mesothelioma patients, 1 was complete remission (CR) and 2 were partial remission (PR). The objective remission rate was 50%; In the patients with PD-L1 positive ≥ 5%, 3 cases achieved objective remission, and the objective remission rate reached 100%; By the time of publication, all the enrolled mesothelioma patients had sustained survival after reinfusion. The longest survival time had reached 22 months. The patients with complete remission had sustained tumor free survival for more than 15 months. The PD-1 nano antibody autocrine by car-t was continuously detected in the peripheral blood of patients with complete remission for 9 months.
Clinical studies have shown that car-t cells that autocrine PD1 nanoantibody mesothelin can bring clinical benefits to patients with relapsed / refractory mesothelioma by reducing tumor burden and prolonging survival, especially those with PD-L1 positive tumors, and achieve tumor clearance and long-term tumor free survival.
Ovarian cancer
The international well-known Journal of Hematology & Oncology published a clinical study on the successful transformation of car-t technology by Chinese medical researchers. The target of car-t product selection mentioned in the study is mesothelin (msln, also known as mesothelin, which can be applied to a variety of epithelial cancers, such as malignant mesothelioma, pancreatic cancer, gastric cancer, ovarian cancer, etc.).
Among them, one patient with advanced pancreatic cancer was treated with intravenous infusion of car-t. after treatment, the metabolic activity of all lesions in the whole body basically disappeared.
Typical case
Subject gd-g/m-005 was a patient with advanced pancreatic cancer with msln expression. The subject progressed to local lymph node metastasis (24 × 33 mm) (Fig. C). Anti msln-7 × 19 car-t cells were first infused through the hepatic artery with high fever that night, without cytokine release syndrome (CRS) or neurotoxicity. Subsequently, he received anti-msln-7 every 1-2 months × 19 intravenous infusion of car-t cells.
Until it increased to 5 times of car-t cell infusion, CT staging showed that he achieved complete remission after 240 days of treatment, and the measured lymph nodes were 8.3 × 9.6mm, and no other enlarged lymph nodes were found (Fig. C). At this time, the focus of the patient completely disappeared and remained normal.