A new strategy for cancer immunocell therapy has been discovered, according to a paper published in Science Translation Medicine by Shanghai Ingda Yang

Recently, the internationally renowned journal Science Translation Medicine published online the latest research results of the research team "A Chimeric antigen receptor with antigen-independent OX40 signaling mediates potent antitumor activity" and was recommended by The Translation Science Medicine magazine online.
the study found for the first time that antigens are not dependent on OX40 signals, providing a new strategy for improving the anti-tumor activity of CAR-T cells and breaking through the challenges of solid tumor therapy.
Yang Caiming of shanghai Jiaozhou University's School of Life Sciences and Technology is the co-author, Dr. Zhang Huihui, Li Fanlin and Dr. Cao Jiang of Xuzhou Medical University are co-authors, and Shanghai Longyao Biotech Co., Ltd. is responsible for the preparation of CAR-T for clinical treatment.
researchers chose to add a full-length costulational subject to the CD3ζCAR (20BBZ CAR) vector, which is currently clinically most widely used, with a single continuous expression of the costulation molecule.
comparing 12 costulation receptors, the researchers found that 20BBZ-OX40 CAR-T cells containing OX40 costulation receptors had better amplification and tumor resistance.
-embedded antigen-insulating antigen-subject T-cell immunotherapy has achieved remarkable results in the treatment of patients with malignant blood tumors, and has also brought great breakthroughs and successes in the field of secondary cell therapy research, but this method has limited efficacy for solid tumor patients, in order to improve the efficacy, the researchers made a variety of improvements to the CAR structure, including series of two co-stimulating molecules, the introduction of CD40L, IL-12, anti-PD-1 immune regulatory molecules and other strategies.
in traditional CAR design, only the in-cell domain of the costulation receptor is used, and when CAR binds to the tumor antigen, the integrated costulation receptor signal is active.
the natural T-cell biopsy process, the biopsy signal of the co-stimulation receptor comes mainly from the co-stimulation complex expressed by the antigen-presenting cell, not from the tumor antigen.
the separation activation strategy of this tumor antigen - the first signal, the total stimulation of the mating body - the second signal provides the unique space-time specificity required for T cell activation.
Shanghai Jiaobo Yang and other team of researchers designed a new CAR-T cell with independent co-stimulation signal, inCAR-T cells alone continuous expression of a co-stimulation body, simulating the second signal of natural T-cell activity, the new CAR-T cell in-body culture model, lotus mouse model, and clinical patient trials showed greater amplification and tumor killing ability.
researchers tested the therapeutic effect of 20BBZ-OX40 CAR-T cells in the Raji and Daudi leukemia models of human B cell origin.
found that compared to traditional 20BBZ-CAR-T cells, 20BBZ-OX40 CAR-T cells had longer survival times in mice with leukemia tumor load.
this is closely related to the better amplification of 20BBZ-OX40 CAR-T cells in the body.
In view of the excellent anti-tumor effect of 20BBZ-OX40 CAR-T cells in mouse models, in order to continue to explore the safety and effectiveness of 20BBZ-OX40 CAR-T cells as clinical anti-tumor therapy, the researchers In cooperation, a preliminary clinical trial was conducted in patients with refractic metastatic B-cell lymphoma, and a total of 5 patients were recruited, all of whom completed 20BBZ-OX40 CAR-T cell therapy with an efficiency of 100%, of which 2 were fully remission and 3 were partially alleviated.
20BBZ-OX40 CAR-T has a very strong amplification capacity in patients, and in one case, their CAR-T cells accounted for more than 80% of T cells at the peak of value-added.
car-T has good safety characteristics, patients do not have CAR-T-related neurotoxic side effects, there is no serious cytokine storm (CRS).
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