"Revolutionizing CAR-T Cell Production with Virus-like Nanovesicles"
In a groundbreaking development, a group of researchers led by Prof. Jun Wang and Prof. Cong-Fei Xu from the School of Biomedical Sciences and Engineering at South China University of Technology has devised an innovative technique for producing CAR-T cells in vivo. The key lies in virus-mimetic fusogenic nanovesicles (FuNV) loaded with anti-CD19 (αCD19) chimeric antigen receptor (CAR) molecules, which seamlessly fuse with T cells, catalyzing the conversion into potent CAR-T cells within the body.
CAR-T cell therapy has demonstrated remarkable success in battling B-cell lymphoma and leukemia. However, the intricate and costly process of manufacturing CAR-T cells has impeded its widespread adoption. This new approach eliminates the need to harvest T cells from patients by directly transferring CAR molecules from FuNVs to T cells. By integrating the CAR protein onto T cells through FuNVs, the risk of complications like cytokine release syndrome and tumorigenicity associated with viral gene integration is mitigated.
The researchers ingeniously engineered T-cell fusogens by combining an anti-CD3 fragment with fusogens from reoviruses or measles viruses. This modification enabled FuNVs derived from these cells to efficiently induce fusion with T cells, both in lab settings and in living organisms. By expressing the fusogen and αCD19 CAR protein in T cells, they produced FuNVs loaded with CARs (FuNVCAR) that successfully generated CAR-T cells in vitro and in vivo. Moreover, intravenous administration of FuNVCAR significantly impeded the growth of B-cell lymphoma.
Extensive toxicity evaluations revealed that FuNVCAR did not induce adverse effects on blood composition, body weight, or inflammatory cytokine levels, unlike traditional CAR-T cell treatments. The transient activation of CAR-T cells produced by FuNVCAR resulted in controlled cytokine release, distinct from the sustained inflammation observed with conventional methods.
This pioneering study heralds a new era in CAR-T cell production, offering a streamlined and safer alternative for patients. While immensely promising, this approach may not be suitable for individuals with compromised T cell functionality. The fusion of cutting-edge nanotechnology with immunotherapy opens doors to more accessible and effective CAR-T cell therapies, bringing us one step closer to revolutionizing cancer treatment.
Source: https://www.eurekalert.org/news-releases/1037834
CAR-T cell therapy has demonstrated remarkable success in battling B-cell lymphoma and leukemia. However, the intricate and costly process of manufacturing CAR-T cells has impeded its widespread adoption. This new approach eliminates the need to harvest T cells from patients by directly transferring CAR molecules from FuNVs to T cells. By integrating the CAR protein onto T cells through FuNVs, the risk of complications like cytokine release syndrome and tumorigenicity associated with viral gene integration is mitigated.
The researchers ingeniously engineered T-cell fusogens by combining an anti-CD3 fragment with fusogens from reoviruses or measles viruses. This modification enabled FuNVs derived from these cells to efficiently induce fusion with T cells, both in lab settings and in living organisms. By expressing the fusogen and αCD19 CAR protein in T cells, they produced FuNVs loaded with CARs (FuNVCAR) that successfully generated CAR-T cells in vitro and in vivo. Moreover, intravenous administration of FuNVCAR significantly impeded the growth of B-cell lymphoma.
Extensive toxicity evaluations revealed that FuNVCAR did not induce adverse effects on blood composition, body weight, or inflammatory cytokine levels, unlike traditional CAR-T cell treatments. The transient activation of CAR-T cells produced by FuNVCAR resulted in controlled cytokine release, distinct from the sustained inflammation observed with conventional methods.
This pioneering study heralds a new era in CAR-T cell production, offering a streamlined and safer alternative for patients. While immensely promising, this approach may not be suitable for individuals with compromised T cell functionality. The fusion of cutting-edge nanotechnology with immunotherapy opens doors to more accessible and effective CAR-T cell therapies, bringing us one step closer to revolutionizing cancer treatment.
Source: https://www.eurekalert.org/news-releases/1037834
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