Efficacy and Safety of Immune Checkpoint Inhibitors in Combination With Engineered Mitochondrial Vaccine as Neoadjuvant and Adjuvant Therapy for Resectable Head and Neck Squamous Cell Carcinoma: A Single-Arm, Single-Center Clinical Study.
Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge, as over 60% of patients are diagnosed at a locally advanced stage with a high risk of recurrence. Although the landmark KEYNOTE-689 trial established neoadjuvant immune checkpoint inhibitor (ICI) therapy as a new standard of care, the pathological complete response (pCR) rate remains unsatisfactory at only 3.0%, highlighting an urgent need for optimized combination strategies. This prospective, single-arm, single-center clinical study aims to evaluate the safety, tolerability, and preliminary efficacy of a novel neoadjuvant and adjuvant regimen combining an engineered mitochondrial vaccine (IMP3-Mito) with ICIs for patients with resectable, IMP3-positive locally advanced HNSCC. The rationale is based on a Prime-and-Release synergistic mechanism: the engineered mitochondrial vaccine serves as a potent natural adjuvant to activate dendritic cells and prime tumor-specific T-cell responses against the IMP3 antigen, while the ICI subsequently releases the immune brakes within the tumor microenvironment. By integrating these two modalities, the study seeks to achieve deeper pathological responses and improve long-term survival, while simultaneously providing clinical evidence for the transformative potential of the mitochondrial engineering platform in overcoming the limitations of conventional tumor vaccines.
• Aged ≥ 18 years, both genders eligible.
• Pathologically confirmed head and neck squamous cell carcinoma (HNSCC) meeting the following criteria:
‣ Clinical stage II-IVB according to the AJCC 8th Edition (nasopharyngeal carcinoma is excluded);
⁃ Positive expression of IMP3 protein;
⁃ Clinically resectable as determined by a Multidisciplinary Team (MDT);
⁃ Subjects must be willing and able to undergo radical surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Adequate organ and bone marrow function, defined as:
‣ Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 80 × 10\^9/L; Hemoglobin (HGB) ≥ 8 g/dL;
⁃ Liver Function: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP) ≤ 2.5 × Upper Limit of Normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN;
⁃ Albumin (ALB) ≥ 2.8 g/dL;
⁃ Renal Function: Serum creatinine (Cr) ≤ 1.5 × ULN or Creatinine Clearance (CCR) \> 60 mL/min;
⁃ Coagulation: International Normalized Ratio (INR) ≤ 1.5; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• Subjects must voluntarily participate in the study, sign the Informed Consent Form (ICF), and be able to comply with the scheduled visits and protocol procedures.