P1, N=29, Not yet recruiting, Sichuan University

Using xenograft mice, we confirmed that CAR-T function could also be inhibited by MSC in vivo and STC1 played a critical role. These data revealed a novel function of MSC and staniocalcin-1 in suppressing CAR-T efficacy, which should be considered in cancer therapy and may also have potential applications in controlling the toxicity arising from the excessive immune response.

Despite the excellent anti-cancer activity, the atezolizumab-based chimeric antigen receptor (CAR) T cells showed a robust off-target effect. Overall, gPD-L1 CAR-T exhibits excellent anti-tumor activity against TNBCs, and it could be a promising immunotherapy tool to treat TNBCs in clinic. Furthermore, targeting glycosylation moiety on the tumor antigen is a novel approach to lessen CAR-T toxicity in patients.

Despite high Tim3 and LAG3 expression in the final manufacturing process, Vax-CAR-T cells significantly suppressed tumor growth in both bigger (>95mm3) and smaller (≤50mm3) AGC xenograft NSG mouse models. More importantly, Vax-CAR-T-treated mice have well tolerated the CAR-T therapy with no significant adverse events during the CRS monitoring period, 2 weeks after Vax-CAR-T injection and have gradually recovered weight gains 5 days after CAR-T cell injection.[Conclusion] We believe that a new autologous CAR-T targeting PD-L1 could be a promising new tool for removing heterogeneous solid tumors in TME, which would be a significant step forward in improving current conventional and immunotherapeutic strategies.

Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

There are researchers questioning the reliability of PAK4 as a drug target, particularly PAK4-related therapy is concerned with the distinguishment of the non-kinase functions and catalytic functions triggered by PAK4 phosphorylation. Meanwhile, synergistic effects of PAK4 inhibitors with PD-1/PD-L1 and CAR-T immunotherapy shed light for the development of PAK4 inhibitors.

Conclusion PET/CT-afforded in vivo tracking of traceable NIS-RFP:CAR‑T enabled quantification of their retention in solid tumours, a parameter crucial to CAR‑T efficacy. We provide a platform enabling highly sensitive non-invasive in vivo PET tracking of CAR‑T thereby addressing a fundamental unmet need in CAR‑T development, and providing the missing information for future clinical imaging.

Conclusion PET/CT-afforded in vivo tracking of traceable NIS-RFP:CAR‑T enabled quantification of their retention in solid tumours, a parameter crucial to CAR‑T efficacy. We provide a platform enabling highly sensitive non-invasive in vivo PET tracking of CAR‑T thereby addressing a fundamental unmet need in CAR‑T development, and providing the missing information for future clinical imaging.

Conclusion PET/CT-afforded in vivo tracking of traceable NIS-RFP:CAR‑T enabled quantification of their retention in solid tumours, a parameter crucial to CAR‑T efficacy. We provide a platform enabling highly sensitive non-invasive in vivo PET tracking of CAR‑T thereby addressing a fundamental unmet need in CAR‑T development, and providing the missing information for future clinical imaging.

Conclusion PET/CT-afforded in vivo tracking of traceable NIS-RFP:CAR‑T enabled quantification of their retention in solid tumours, a parameter crucial to CAR‑T efficacy. We provide a platform enabling highly sensitive non-invasive in vivo PET tracking of CAR‑T thereby addressing a fundamental unmet need in CAR‑T development, and providing the missing information for future clinical imaging.

The key immunosuppressive mechanism is the expression of PD-1/PD-L1. We used gene silencing technique mediated by shRNA (short hair RNA) to block the PD-1/PD-L1 pathway in lymphoma and prostate tumors, thus enhancing the anti-tumor effect of CAR-T cells on subcutaneous xenograft.

P1, N=16, Active, not recruiting, NantKwest, Inc. | Recruiting --> Active, not recruiting

Enrollment into Cohort 2 began December 2019. Research Funding: NantKwest