CELL INTELLIGENCE · 肿瘤细胞治疗研究

1. Procurement Eligibility

   Inclusion Criteria:
   * Diagnosis of a solid tumor expressing GPC3
   * Karnofsky score of \>=60%
   * Life expectancy of \>16 weeks
   * Informed consent explained to, understood by and signed by participant or participant's legally authorized representative

   For patients with hepatocellular carcinoma only:
   * Barcelona Liver Cancer Stage A, B or C
   * Child-Pugh-Turcotte Score \<7

   Exclusion Criteria:
   * History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.

     * History of organ transplantation
     * Known HIV positivity
     * Active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
2. Treatment eligibility

Inclusion Criteria:

* Karnofsky score of \>=60%
* Life expectancy of \>16 weeks
* Informed consent explained to, understood by and signed by patient/guardian.
* Adequate organ function
* Adequate laboratory values
* Refractory or relapsed disease after treatment with up- front therapy and at least one salvage treatment cycle
* Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
* Informed consent explained to, understood by and signed by patient/guardian.

For patients with hepatocellular carcinoma only:

* Barcelona Liver Cancer Stage A, B or C
* Child-Pugh Turcotte Score \<7

Exclusion Criteria:

* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.

  * History of organ transplantation
  * Known HIV positivity
  * Active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
* Pregnancy or lactation
* Systemic steroid treatment (≥ 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24hrs prior to CAR T cell infusion)

主要终点：The number of successfully manufactured SC-CAR.GPC3xIL15.21 T cell products will be assessed · The proportion of SC-CAR.GPC3xIL15.21 T cell products that are approved for release after up to 2 grow attempts will be measured. · 28 days；To determine the safety of escalating doses of an intravenous injection of SC-CAR.GPC3xIL15.21 T cells in adults with relapsed or refractory GPC3-positive solid tumors after lymphodepleting chemotherapy based on frequency of adverse events based on CTCAE · The type, frequency, severity, and duration of adverse events will be tabulated and summarized · 42 days
次要终点：To determine the maximum tolerated dose (MTD) of SC-CAR.GPC3xIL15.21 T cells in treating patients with GPC3-positive solid tumors after lymphodepleting chemotherapy.；To assess the response rate in patients with relapsed or refractory GPC3-positive solid tumors infused with SC-CAR.GPC3xIL15.21 T cells.

• SC-CAR.GPC3xIL15.21 T cells · EXPERIMENTAL · Autologous SC-CAR.GPC3xIL15.21 T cell product infused as a single infusion.

This Phase 1, open-label, non-randomized study will enroll adult subjects with relapsed or refractory non-central nervous system (CNS) malignant solid tumors expressing glypican-3 (GPC3) to examine the safety, feasibility, and efficacy of administering T cell products derived from peripheral blood mononuclear cells (PBMC) that have been genetically modified to co-express a GPC3-specific chimeric antigen receptor (CAR), interleukin (IL)-15 and IL-21 as well as the inducible caspase 9 (iC9) suicide gene (SC-CAR.GPC3xIL15.21 T cells). An adult participant meeting all eligibility criteria and meeting none of the exclusion criteria will have a blood sample collected, which will be used to bioengineer the CAR T cells targeting their tumor.