Cancer-associated fibroblasts (CAFs), as core regulators within the tumor microenvironment, significantly impede the intratumoral penetration of therapeutic agents and suppress the effective infiltration and activation of immune cells by constructing elaborate physical and functional barriers. Fibroblast activation protein (FAP) is a highly specific therapeutic target for CAFs, owing to its nearly tumor-restricted expression profile. Therefore, developing therapeutic strategies that specifically target FAP to eliminate CAFs and subsequently remodel the tumor microenvironment may effectively disrupt the multi-dimensional defense system established by CAFs, thereby significantly enhancing the delivery efficiency of anti-tumor agents and improving responsiveness to immunotherapy.
This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of FAP mRNA Vaccine combined with immune checkpoint inhibitors in patients with advanced malignant solid tumors.
1. Male or female patients: aged ≥ 18 years old;
2. Patients with histopathologically confirmed advanced malignant solid tumors (such as patients with advanced lung cancer, advanced colorectal cancer, advanced pancreatic carcinoma, etc.);
3. Patients refractory or intolerant to standard clinical treatment regimens;
4. According to the RECIST 1.1 criteria, at least one measurable lesion is required;
1. History of other malignancies, except for adequately treated and non-recurrent within 5 years prior to screening basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal mucosal carcinoma, which the investigator deems eligible for inclusion;
2. Known central nervous system (CNS) metastases that are untreated or not effectively controlled by prior therapy;
3. Patients with serious cavity effusion;
4. Patient has comorbid conditions associated with elevated FAP expression beyond solid tumors, including pulmonary fibrosis, liver fibrosis, renal fibrosis, and rheumatoid arthritis, etc.;