Treatment of Advanced Endocrine Tumor With Iindividualized mRNA Neoantigen Vaccine (mRNA-0523-L001)

Inclusion Criteria:

1. The subjects voluntarily sign the written informed consent form and can comply withthe visits and related procedures specified in the protocol;

2. The subjects are 18 years old or older, regardless of gender;

3. Patients with advanced endocrine tumors confirmed by histology or cytology in thepast 6 months (including medullary thyroid carcinoma, thymic carcinoma and adrenalcortical carcinoma, etc.), who have failed standard treatment or have no standardtreatment available;

4. No HLA-related genes or chromosomal regions with copy number variations (CNVs) orloss of heterozygosity (LOH) were detected by gene sequencing;

5. They have advanced or metastatic lesions confirmed by immunohistochemistry, and havefrozen tissue/cells sufficient for WES and RNAseq sequencing, and afterbioinformatics analysis, they predict at least one antigen that is effectivelypresented by their own HLA, such as KRAS or TP53 mutations and corresponding HLAtyping, see 1.4 for the rationale of the topic.

6. Expected survival ≥ 4 months;

7. According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), theyhave at least one measurable lesion, which should not have received local treatmentsuch as radiotherapy (lesions in the previous radiotherapy area, if confirmed tohave progressed, can also be selected as target lesions);

8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1;

9. They have not used granulocyte colony-stimulating factor (G-CSF),granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood celltransfusion or platelet transfusion within 14 days before the examination.

10. Subjects of childbearing potential (male and female) who meet the inclusion criteriamust agree to use reliable contraception methods (hormonal or barrier methods orabstinence) during the trial and for at least 90 days after the last administration;women of childbearing age must have a negative blood pregnancy test within 7 daysbefore the first administration.

11. Virology test: No CMV, EBV, HIV, HBV, HCV, syphilis infection (only at baseline)

Exclusion Criteria:

1. Received chemotherapy, hormone therapy, traditional Chinese medicine with anti-tumorindications or other anti-tumor treatments within 4 weeks before the firstadministration (for mitomycin and nitrosourea, the last administration was within 6weeks before the first administration of this study drug), or within 5 half-lives ofimmunotherapy or molecular targeted therapy;

2. Received other major surgery other than diagnosis or biopsy within 4 weeks beforethe first administration, or expected to receive major surgery during the study;

3. Patients who have received allogeneic hematopoietic stem cell transplantation ororgan transplantation in the past, or plan to receive organ transplantation duringthis study;

4. Patients who have received other tumor vaccines or cell therapies in the past;Medical condition

5. Patients with clinically symptomatic brain metastases, spinal cord compression,carcinomatous meningitis, or other evidence indicating that the patient's brain orspinal cord metastases are not controlled, and are deemed unsuitable for enrollmentby the investigator;

6. In the past 2 years, there have been known other malignant tumors that areprogressing or require active treatment (except for non-melanoma skin cancer,superficial bladder cancer, and cervical carcinoma in situ that have been cured byradical surgery);

7. Have a history of interstitial lung disease (ILD) or pulmonary interstitialfibrosis;

8. Have a history of severe cardiovascular and cerebrovascular diseases, including butnot limited to: a) Have severe cardiac rhythm or conduction abnormalities, such asventricular arrhythmias requiring clinical intervention, II-III degreeatrioventricular block; corrected QTc interval male > 450 milliseconds, female > 470milliseconds, b) Acute coronary syndrome, congestive heart failure, aorticdissection, stroke or other grade 3 or higher cardiovascular and cerebrovascularevents occurred within 6 months before the first administration, c) New York HeartAssociation (NYHA) ≥ III grade heart failure or left ventricular ejection fraction (LVEF) <50%.

9. Other serious and/or uncontrollable diseases that may affect the subject'sparticipation in this study, as determined by the investigator, including but notlimited to: a) Have a history of severe drug allergy, or known to be allergic to anycomponent of the tumor vaccine; or have had a severe allergic reaction to othermonoclonal antibodies in the past, b) Have a history of immunodeficiency, includingHIV positive or other acquired or congenital immunodeficiency diseases, c) Evidenceof severe or uncontrolled liver or kidney disease, d) Poorly controlledhypertension, diabetes, etc., e) Patients with active ulcers or gastrointestinalbleeding f) Have a severe infection that requires intravenous infusion ofantibiotics or hospitalization; or uncontrolled active infection within 4 weeksbefore the first administration, g) Have active syphilis infection.

10. Participated in other clinical trials within 4 weeks before the first administration (except for screening failure);

11. Currently receiving systemic use of corticosteroids (except for recent or currentuse of inhaled corticosteroids);

12. Pregnant or lactating women; Laboratory and imaging examinations

13. Imaging (CT or MRI) shows that the tumor invades the large blood vessels and has atendency to bleed;

14. Have clinically significant thyroid function abnormalities, and the investigatordeems them unsuitable for enrollment;

15. Active pneumonia was found in the screening chest CT scan;

16. Uncontrolled pleural effusion, pericardial effusion, or ascites that requiresrepeated drainage;

17. The adverse reactions of previous anti-tumor treatment have not recovered toNCI-CTCAE 5.0 grade evaluation ≤ 1 (except for hair loss);

18. Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B virusdeoxyribonucleic acid (HBV DNA) test value higher than the upper limit of normal;hepatitis C virus antibody (HCV Ab) positive and HCV RNA test value higher than theupper limit of normal; Investigator assessment

19. The investigator considers that there are other reasons that are not suitable forparticipating in the clinical trial.