CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Male, age ≥18 years, with life expectancy ≥6 months.
* Histologically confirmed prostate adenocarcinoma with documented metastatic disease (bone, lymph nodes, or visceral organs) by recent whole-body MRI, bone scintigraphy (ECT), or PSMA-PET/CT.
* Confirmed metastatic castration-resistant prostate cancer (mCRPC) with documented disease progression after ≥1 line of novel endocrine therapy (e.g., abiraterone or enzalutamide).
* ECOG performance status 0-1.
* Availability of tumor tissue (fresh biopsy or archival specimen) for neoantigen screening.
* Willingness to undergo long-term follow-up.
* Provision of signed informed consent form by participant or legally authorized representative prior to study procedures.
* Willingness to undergo prostate biopsy if required for tissue acquisition. Adequate organ function as defined by laboratory values at screening: Absolute neutrophil count (ANC) \>1.5×10⁹/L; Platelet count \>100×10⁹/L; Hemoglobin \>90 g/L; Total bilirubin, ALT, and AST within normal laboratory limits; Serum creatinine \<133 μmol/L (or \<1.5 mg/dL); INR \<1.3 (or \<3.0 if on warfarin or other anticoagulants); Albumin \>30 g/L; Left ventricular ejection fraction (LVEF) ≥45% Negative for HIV, HBV (HBV DNA ≤500 IU/mL acceptable), and HCV (HCV RNA negative); No clinically significant ECG abnormalities.

Exclusion Criteria:

* History of other malignancies within the past 5 years (except non-melanoma skin cancer or carcinoma in situ with documented disease-free survival \>5 years).
* Symptomatic central nervous system metastases.
* Uncontrolled active or persistent infection requiring systemic therapy.
* Systemic corticosteroid therapy within 4 weeks prior to enrollment (equivalent to \>20 mg/day prednisone).
* Prior immunomodulatory therapy within 3 months, including but not limited to IL-2, CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, CD40 agonists, or CD137 agonists (except adjuvant IFN-α for high-risk melanoma).
* Prior investigational prostate cancer-targeted vaccine therapy or cellular therapy within 3 months.
* Receipt of other investigational products within 2 months prior to enrollment.
* Known, confirmed, or suspected autoimmune disease or immunosuppressive condition.
* History of severe allergic reaction to any prior vaccination (for infectious disease prevention).
* Major cardiovascular events within 6 months prior to first dose, including acute coronary syndrome, aortic dissection, or stroke; or presence of severe cardiovascular disease requiring clinical intervention.
* Active autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus).
* Receipt of live vaccines within 4 weeks prior to first study treatment or planned during the study period.
* Uncontrolled hypertension (despite optimal medical management).
* Substance abuse or any psychological condition that, in the investigator's judgment, may interfere with study participation or results.
* Investigator's assessment of insufficient compliance or presence of other severe systemic diseases that would make the participant unsuitable for the study.
* High tumor burden as assessed by imaging, deemed unsuitable by the investigator.

主要终点：Incidence of Dose-Limiting Toxicities (DLTs) · Number of participants experiencing Dose-Limiting Toxicities (DLTs) during the first 4 weeks (following 2 doses) of treatment. This is evaluated per the 3+3 dose-escalation design to assess the safety and tolerability of the autologous neoantigen-pulsed dendritic cell vaccine (YS247) in mCRPC patients. · From first dose through 60 days after the last dose (up to approximately 3 months)；Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) · Number of participants experiencing treatment-emergent adverse events (TEAEs), including specifically Grade ≥3 TEAEs, serious adverse events (SAEs), and immune-related adverse events. The severity of all adverse events will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. · From first dose through 60 days after the last dose (up to approximately 3 months)；Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) · Determination of the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of the autologous neoantigen-pulsed dendritic cell vaccine (YS247). The MTD and RP2D will be determined based on the assessment of Dose-Limiting Toxicities (DLTs) observed during the dose-escalation phase. · From first dose through 60 days after the last dose (up to approximately 3 months)
次要终点：Prostate-Specific Antigen (PSA) Response Rate (PSA50)；Progression-Free Survival (PFS)；Objective Response Rate (ORR)；Disease Control Rate (DCR)；Duration of Response (DOR)；Neoantigen-Specific T-cell Immune Response；Tumor-Infiltrating Lymphocyte (TIL) Density；Overall Survival (OS)

• YS247 (Neo-DC) Vaccine Therapy · EXPERIMENTAL · Single-arm study of autologous neoantigen-pulsed dendritic cell vaccine (YS247) administered via subcutaneous injection. The study employs a 3+3 dose-escalation design with three sequential cohorts: Low dose (5×10⁶ cells), Medium dose (1×10⁷ cells), and High dose (1.5×10⁷ cells) per injection. Participants receive the vaccine every 2 weeks for a total of 4 doses (8-week treatment period). Injections are delivered at 1-3 sites (axillary or inguinal regions) per dose. Each injection site receives 0.3 mL of cell suspension containing the designated dose level.

This phase I study tests a personalized cancer vaccine (Neo-DC) for men with advanced prostate cancer (metastatic castration-resistant prostate cancer, or mCRPC) that has continued to grow despite standard hormone therapies and other treatments. The vaccine is custom-made for each participant using their own immune cells (dendritic cells) mixed with specific tumor markers (neoantigens) unique to their cancer. These neoantigens are identified through genetic sequencing of the patient's tumor. The goal is to help the body's immune system recognize and attack the cancer cells specifically. The study will enroll approximately 9 to 18 men and will test three different dose levels to find the safest amount. Participants will receive the vaccine as an injection under the skin every two weeks for a total of 4 doses over an 8-week treatment period. The main purpose is to evaluate the safety of this vaccine, determine the maximum tolerated dose, and identify any serious side effects. Researchers will also look at whether the vaccine helps lower PSA levels (a blood marker for prostate cancer), slows cancer growth, and stimulates an immune response against the tumor. Participants will be monitored closely during treatment and followed for several months afterward to assess long-term safety and effects.