Title : Phase I dose-escalation study of nanobody-armored Dendritic Cell Vaccine (Baize DC) in patients with solid tumors after radical resection
Abstract:
Background and Objective: Conventional dendritic cell (DC) vaccines face limitations including immunosuppressive lymph node microenvironment and low tumor antigen immunogenicity. In an early investigator-initiated trial (IIT), a total of 805 post-surgical patients treated with a DC2.0 plus vaccine demonstrated 98.6% grade 1 adverse events, 54.8% T cell response rate, and 96.0% 1-year recurrence-free survival (RFS). Baize DC is an upgraded next-generation vaccine candidate (SHC1001) derived from DC2.0 plus, employing a proprietary technology enabling DCs to secrete PD-1/CTLA-4 antibodies and load four antigens including P53 and KRAS. This phase I dose-escalation study (NCT07479667) was initiated to evaluate its safety, impact on MRD (ctDNA), bispecific antibody pharmacokinetics, and antigen-specific T cell responses in patients after radical resection.
Methods: Eight patients were enrolled in this dose-escalation study after R0/R1 resection and had completed adjuvant chemotherapy. Tumor types included colorectal cancer (n=2), gastric cancer (n=2), and pancreatic cancer (n=4). Baize DCs were administered as a single subcutaneous injection at four dose levels: 1.5×10? (n=3), 4.5×10? (n=3), 9.0×10? (n=1), and 1.8×10? cells/dose (n=1). The primary endpoint was safety; secondary endpoints included bispecific antibody pharmacokinetics, T cell responses, and MRD monitoring (ctDNA).
Results: All 8 patients received a single dose of Baize DC vaccine candidate injection.
(1) Safety: Adverse events occurred in only 2 patients (dry mouth, hyperhidrosis), both at grade 1. No higher grades (≥2) were observed with treatment-related adverse events.
(2) MRD Monitoring: Of the first 4 evaluable patients, two were MRD-positive and two were MRD-negative at baseline. Both MRD-positive patients had pancreatic cancer (one from dose Level 2, one from dose Level 4). Post-injection, both patients showed favorable ctDNA dynamics: the Level 2 patient demonstrated continuous VAF decline, and the Level 4 patient converted to MRD-negative. Among MRD-negative patients, one transiently became ctDNA-positive at 2 months but reverted at 3 months, while the other maintained ctDNA-negative status throughout.
(3) Bispecific Antibody Pharmacokinetics: Plasma concentrations peaked at Day 2 in all 4 evaluable patients, ranging from 20.50 to 43.67 pg/mL, with no dose-dependent relationship observed.
(4) Antigen-Specific T Cell Responses: Three of 4 evaluable patients (75%) showed positive ELISPOT responses. At Day 14, JL0102 responded to multiple antigens (SI: KRAS 57.6, P53 58.9, TERT 30.8,), and JL0103 showed P53 response (SI 12.9). At Day 21, JL0101 exhibited P53 response (SI 23.5). JL0104 remained negative.
Conclusion: SHC1001, a nanobody-armored Baize DC vaccine candidate, achieved excellent safety (no adverse event grade ≥2) and promising immunogenicity and MRD dynamics. The vaccine enhances immunogenicity through autocrine checkpoint antibodies and mRNA antigen loading. Notably, both MRD-positive pancreatic cancer patients showed marked ctDNA decline post-vaccination. Given the high post-surgical recurrence rate of pancreatic cancer and these encouraging signals, future efforts will prioritize enrolling more pancreatic cancer patients in a planned Phase II study.
