CELL INTELLIGENCE · 肿瘤细胞治疗研究

1. Procurement Eligibility

   Inclusion Criteria:
   * Diagnosis of a solid tumor expressing GPC3
   * Lansky or Karnofsky score of \>=60%
   * Life expectancy of \>16 weeks
   * 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)
2. Treatment eligibility

Inclusion Criteria:

* Lansky or 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 12 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 autoimmune or inflammatory disorder
* Live vaccines within 30 days prior to enrollment

  • Active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
* Pregnancy or lactation
* Uncontrolled infection
* 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)
* Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.

主要终点：The number of successfully manufactured SC-CAR.GPC3xIL15.21 T cell products will be assessed · The number of successfully manufactured products will be measured · 28 days；Establish the safety, defined by adverse events of SC-CAR.GPC3xIL15.21 T cells. · Type, frequency, severity, and duration of adverse events will be tabulated and summarized · 28 days
次要终点：Estimate the maximum tolerated dose (MTD) or biologically effective dose and dose limiting toxicities (DLT), and describe the full toxicity profile of SC-CAR.GPC3xIL15.21 T cells.；To estimate anti-tumor responses by measuring changes in tumor burden using disease-specific evaluations following SC-CAR.GPC3xIL15.21 T cells.

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

This Phase 1, open-label, non-randomized study will enroll pediatric and young 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). A child or young adult 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.