Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma
Open Access
- 5 January 2017
- journal article
- case report
- Published by Springer Science and Business Media LLC in Journal of Hematology & Oncology
- Vol. 10 (1), 1-11
- https://doi.org/10.1186/s13045-016-0378-7
Abstract
Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far. In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone. This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation. ClinicalTrials.gov NCT01869166 and NCT02541370.Keywords
This publication has 38 references indexed in Scilit:
- Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapyNature Reviews Cancer, 2016
- Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach?Nature Reviews Clinical Oncology, 2016
- PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinationsScience Translational Medicine, 2016
- Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?Journal of Cellular Physiology, 2015
- Recent advances for the treatment of pancreatic and biliary tract cancer after first-line treatment failureExpert Review of Anticancer Therapy, 2015
- Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor ActivityCancer Research, 2015
- Targeted Therapy in Biliary Tract CancersCurrent Treatment Options in Oncology, 2015
- Blockade of PD-1 immunosuppression boosts CAR T-cell therapyOncoImmunology, 2013
- Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapyLung Cancer, 2012
- Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting CancerClinical Cancer Research, 2012