CAR T Cell Receptor Immunotherapy Targeting Mesothelin for Patients With Metastatic Cancer

Summary

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patients white blood cells with a retrovirus that has the gene for anti-mesothelin incorporated in the retrovirus. Objective: The purpose of this study is to determine a safe number of these cells to infuse and to see if these tumor fighting cells (anti-mesothelin cells) cause metastatic cancer tumors to shrink. Eligibility: \- Adults age 18-70 with metastatic cancer expressing the mesothelin molecule. Design: Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-mesothelin cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-mesothelin cells, and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Timeline

Start

2012-05-04

Primary completion

2018-12-17

Completion

2018-12-17

Publications

• Background Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC, Pastan I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007 Sep 1;13(17):5144-9. doi: 10.1158/1078-0432.CCR-07-0869.
• Background Chang K, Pai LH, Pass H, Pogrebniak HW, Tsao MS, Pastan I, Willingham MC. Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. Am J Surg Pathol. 1992 Mar;16(3):259-68. doi: 10.1097/00000478-199203000-00006.
• Background Hassan R, Cohen SJ, Phillips M, Pastan I, Sharon E, Kelly RJ, Schweizer C, Weil S, Laheru D. Phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009 in patients with mesothelin-expressing cancers. Clin Cancer Res. 2010 Dec 15;16(24):6132-8. doi: 10.1158/1078-0432.CCR-10-2275. Epub 2010 Oct 29.

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