Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma

Background: Mesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN. Objective: To test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma. Eligibility: People aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment. Design: Participants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN. Participants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. Participant s T cells will be modified in a lab to produce TNhYP218 CAR T cells. Participants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment. TNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days. After discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy. Long-term follow-up will continue another 10 years....

* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria. For this protocol, treatment initiation is defined as the first day of lymphodepleting chemotherapy. * Participant must have unresectable, locally advanced, or metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors. For participants with mesothelioma only those with epithelioid or biphasic histology (with \>80% epithelioid component) will be eligible. The diagnosis will be confirmed by the Laboratory of Pathology, CCR, NCI. * Participant must have progressed on at least one FDA-approved systemic therapy considered standard of care for their tumor type. There is no limit on the number of prior treatment regimens. Note: Given the aggressive nature of pancreatic cancer, otherwise eligible individuals with this cancer type can undergo leukapheresis before or while they are getting their frontline treatment as long as they meet all other inclusion criteria. However, TNhYP218 CAR T cells will only be administered after progression on first line standard of care therapy. * Participant must have at least 1 measurable lesion by RECIST version 1.1. * Tumor must have MSLN positivity of 2+ to 3+ in \>= 50% cancer cells by immunohistochemistry on freshly collected biopsy or archival tissue. * Age \>= 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participants must have adequate organ and marrow function as defined below: System: Laboratory Value Hematological * Hemoglobi: \>=9 g/dL(a) * absolute neutrophil count: \>=1,500/mcL * platelets: \>=100,000/mcL Hepatic * total bilirubin: \1.5 X ULN * AST and ALT \ 470 msec in females (\> 80 msec for participants with bundle branch block). Either Fridericia s or Bazett s formula may be used to correct the QT interval. * Participant has active infection with HIV, hepatitis B virus, HCV, or HTLV as defined below: * Positive serology for HIV, HTLV-1, or HTLV-2. * Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Participants who are hepatitis B surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. * Active hepatitis C infection as demonstrated by hepatitis C RNA test. Participants who are HCV antibody positive will be screened for HCV RNA by any reverse transcription PCR or branched DNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value. * Participant is pregnant or intends to be pregnant during the required period of contraception for participants of childbearing potential. * Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of treatment initiation * Participants with a history of seizure disorder unless due to now treated metastatic lesions. * Ongoing uncontrolled intercurrent illness, including but not limited to ongoing or active infection, that would impact participant safety or limit compliance with study requirements.