Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Patients With Advanced Esophageal Cancer and Non-small Cell Lung Cancer

Inclusion Criteria:

* Aged between 18 and 75 (including both ends), with no gender limit;
* The primary lesion was confirmed by histopathology or cytology as esophageal carcinoma (ⅢC (T4bNanyM0, TanyN3M0), and stage Ⅳ) or non-small cell lung cancer (stage ⅢB-Ⅳ).
* Patients who have metastatic or locally advanced tumor but failed instandard treatments or not suitable for standard treatments;
* According to RECIST (V1.1), the efficacy evaluation criteria for solid tumors, there is at least one measurable lesion.
* Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS
* Participants must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry
* Fertile patients must agree to use a reliable contraceptive methods (hormonal or barrier methods or abstinence) during the trial and for at least 12 weeks after the last treatment;
* The subject voluntarily participates and signs ICF (Informed consent forms).

Exclusion Criteria:

* Any clinical research drugs, anti-cancer monoclonal antibodies, anti-cancer therapeutic vaccines, immunostimulants (such as IL-2) or using previous investigational drugs within 7 days of the first treatment with mRNA-personalized tumor vaccine or carrelizumab.
* Patients who have allergies or previous history of biological drug allergy;
* Patients who are in pregnant or breast-feeding;
* Patients who are expected to survive less than 3 months during the screening period;
* Tumor mutation load (TMB) is less than 2.0/Mb or tumor neogenic antigen load (TNB) is less than 0.5/Mb or the number of predicted neoantigen is less than 3;
* Patients who underwent major surgery or suffered significant trauma within 4 weeks prior to the enrollment (blood collection), or who are expected to undergo major surgery during the study period;
* Patients with symptoms of brain metastases (Patients with stable brain metastases can be included)
* Extensive lung metastases from tumors, causing breathing difficulties;
* Patients who have tumors close to large blood vessels or nerves;
* A history of severe cardiovascular and cerebrovascular diseases, including but not limited to ventricular arrhythmia requiring clinical intervention; Acute coronary syndrome, myocardial infarction, congestive heart failure, stroke or other grade III and above cardiovascular events within 6 months; New York Heart Association (NYHA) cardiac function grade≥Grade II or left ventricular ejection fraction (LVEF) \<50%; Poorly controlled hypertension after standard treatment (systolic blood pressure\> 150 mmHg and diastolic blood pressure\> 90 mmHg);
* Patients with active ulcers and gastrointestinal bleeding;
* Patients with clinically confirmed autoimmune disease have received systemic treatment in the past 2 years; HIV, HCV positive; HBV-DNA≥1×103 copies/mL (or 2×102 IU/mL); Acute EBV or CMV virus infection;
* Patients with previous history of non-infectious pneumonia requiring steroid therapy or acute lung cancer;
* Participants with a history of interstitial lung disease;
* Patients who have a history of organ transplantation or are waiting for organ transplantation;
* Have any uncontrolled active infection;
* Immunosuppressed subjects, including those with known immunodeficiency; those who are currently using steroids systemically (except those who are using inhaled steroids recently or currently);
* Skin diseases (such as psoriasis) may prevent intradermal vaccines from reaching the target area;
* Who have received chemotherapy, biotherapy, radiotherapy, endocrine therapy, targeted therapy and other tumor treatments, or other experimental drug treatments, or surgery (excluding diagnostic biopsy) within 7 days prior to the first administration of mRNA tumor vaccine treatment;
* Adverse effects from previous antitumor therapy have not recovered referred to CTCAE (V5.0) rating ≤1 (except hair loss);
* The investigator evaluates that the subject is unable or unwilling to comply with the requirements of study protocol.