Received: 19 January 2017
|
Accepted: 5 March 2017
DOI: 10.1002/jso.24627
REVIEW ARTICLE
CAR T-cell therapy for pancreatic cancer Carl J. DeSelm MD, PhD1 | Zachary E. Tano MD2 | Anna M. Varghese MD3 | Prasad S. Adusumilli MD, FACS, FCCP1,2 1 Center
for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York
Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a
2 Thoracic
patient’s own T cells to target cancer cells. The remarkable results in hematological malignancies
Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
3 Gastrointestinal
prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of
Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities,
Correspondence Prasad S. Adusumilli, MD, FACS, FCCP, Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Email: [email protected]
KEYWORDS
challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy.
adoptive cell therapy, CAR T cells, chimeric antigen receptor, checkpoint blockade, immunotherapy
Funding information Memorial Sloan-Kettering Cancer Center, Grant number: GC228760; Stand Up To Cancer, Grant number: SU2C-AACR-DT1012; National Cancer Institute, Grant number: P30CA008748; Congressionally Directed Medical Research Programs, Grant numbers: BC132124, LC110202, PR101053
1 | INTRODUCTION
remission (CR) was seen in up to 22% of patients with metastatic disease.8 TIL therapy relies on the ability to isolate and expand tumor-
Pancreatic ductal adenocarcinoma (PDAC), the most common type of
reactive T cells from within the patient tumor, which is challenging to
pancreatic cancer, is projected to become the second leading cause of
implement. Progress in genetic engineering and a greater understand-
cancer death in the United States by 2030.1 Despite recent advances
ing of T-cell biology have allowed us now to translate the complex
in systemic chemotherapy for metastatic PDAC with approval of
cytotoxic T-cell response into a synthetic molecule that can be
several chemotherapy regimens in the last decade, median overall
introduced into T cells. Adoptive cell therapy using genetically
survival remains poor for this disease (
|
Accepted: 5 March 2017
DOI: 10.1002/jso.24627
REVIEW ARTICLE
CAR T-cell therapy for pancreatic cancer Carl J. DeSelm MD, PhD1 | Zachary E. Tano MD2 | Anna M. Varghese MD3 | Prasad S. Adusumilli MD, FACS, FCCP1,2 1 Center
for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York
Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a
2 Thoracic
patient’s own T cells to target cancer cells. The remarkable results in hematological malignancies
Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
3 Gastrointestinal
prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of
Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities,
Correspondence Prasad S. Adusumilli, MD, FACS, FCCP, Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065. Email: [email protected]
KEYWORDS
challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy.
adoptive cell therapy, CAR T cells, chimeric antigen receptor, checkpoint blockade, immunotherapy
Funding information Memorial Sloan-Kettering Cancer Center, Grant number: GC228760; Stand Up To Cancer, Grant number: SU2C-AACR-DT1012; National Cancer Institute, Grant number: P30CA008748; Congressionally Directed Medical Research Programs, Grant numbers: BC132124, LC110202, PR101053
1 | INTRODUCTION
remission (CR) was seen in up to 22% of patients with metastatic disease.8 TIL therapy relies on the ability to isolate and expand tumor-
Pancreatic ductal adenocarcinoma (PDAC), the most common type of
reactive T cells from within the patient tumor, which is challenging to
pancreatic cancer, is projected to become the second leading cause of
implement. Progress in genetic engineering and a greater understand-
cancer death in the United States by 2030.1 Despite recent advances
ing of T-cell biology have allowed us now to translate the complex
in systemic chemotherapy for metastatic PDAC with approval of
cytotoxic T-cell response into a synthetic molecule that can be
several chemotherapy regimens in the last decade, median overall
introduced into T cells. Adoptive cell therapy using genetically
survival remains poor for this disease (
