CAR T-Cell-Based Combination Therapy for Pancreatic Ductal Adenocarcinoma (PDAC)

Authors

  • Yi Xing

DOI:

https://doi.org/10.54097/q7777040

Keywords:

Cancer, Chimeric antigen receptor, Chemotherapy, Radiotherapy, Immunotherapy.

Abstract

It is projected that by 2030, following the lung cancer, pancreatic cancer will rank among the deadliest cancers. Because of the limited initial symptoms and early diagnosis, PDAC has one of the most dismal prognosis among all types of malignancies. Therefore, it is crucial to develop promising treatments for PDAC cases. Genetically engineering the T lymphocytes to express designed chimeric antigen receptors (CAR) is an emerging direction, but the major hindrance is the complex tumor microenvironment (TME) that restricts its performance. This review paper discusses the existing combinations between CAR T-cell and other therapies, the challenges, and future improvements in promoting the therapeutic outcomes of PDAC. Multiple chemotherapeutic drugs remodel the complicated TME to upregulate the potency of T cells. Some radiotherapies augment tumor-associated antigen expression to increase the anticancer activities. Additionally, the cytotoxicity of the engineered T cells is enhanced by checkpoint inhibitor blockade (CPB). Oncolytic viruses (OVs) represent another novel approach in CAR T-cell combination. OVs stimulate cytokines, which then trigger the chemokines in CAR-T-cell regulations. Being well-versed in the potential concurrent therapies in CAR T-cell-based manner facilitates researchers in conducting future studies in a more targeted way towards PDAC. 

Downloads

Download data is not yet available.

References

Rahib L, Smith BD, Aizenberg R, et al. Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States. Cancer Research, 2014, 74(11): 2913-2921.

Wood LD, Canto MI, Jaffee EM, et al. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis and Treatment. Gastroenterology, 2022, 163(2): 386-402.

Basturk O, Hong SM, Wood LD, et al. A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas. The American journal of surgical pathology, 2015, 39(12): 1730-1741.

Helms E, Onate MK, Sherman MH. Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment. Cancer Discovery, 2020, 10(5): 648-656.

Elyada E, Bolisetty M, Laise P, et al. Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts. Cancer Discovery, 2019, 9(8): 1102-1123.

Chen PT, Wu T, Wang P, et al. Pancreatic Cancer Detection on CT Scans with Deep Learning: A Nationwide Population-based Study. Radiology, 2022, 306(1): 172-182.

Cutmore LC, Brown NF, Raj D, et al. Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma. Pancreatology, 2020, 20(3): 394-408.

Akce M, Zaidi MY, Waller EK, et al. The Potential of CAR T Cell Therapy in Pancreatic Cancer. Frontiers in Immunology, 2018, 9: 2166.

Morrison AH, Byrne KT, Vonderheide RH. Immunotherapy and prevention of pancreatic cancer. Trends in cancer, 2018, 4(6): 418-428.

DeSelm CJ, Tano ZE, Varghese AM, et al. CAR T-cell therapy for pancreatic cancer. Journal of Surgical Oncology, 2017, 116(1): 63-74.

Arthur Xuan Wang, Xiao Jing Ong, Criselle D'Souza, et al. Combining chemotherapy with CAR-T cell therapy in treating solid tumors. Frontiers in Immunology, 2023, 14: 1140541.

Zhao Z, Xiao X, Saw PE, et al. Chimeric antigen receptor T cells in solid tumors: a war against the tumor microenvironment. Science China Life Sciences, 2019, 63(2): 180-205.

Enblad G, Karlsson H, Gammelgård G, et al. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clinical Cancer Research, 2018, 24(24): 6185-6194.

Al-Haideri M, Tondok SB, Safa SH, et al. CAR-T cell combination therapy: the next revolution in cancer treatment. Cancer Cell International, 2022, 22(1): 1-26.

Anurathapan U, Chan RC, Hindi HF, et al. Kinetics of tumor destruction by chimeric antigen receptor-modified T cells. Molecular Therapy: The Journal of the American Society of Gene Therapy, 2014, 22(3): 623-633.

Zhong L, Li Y, Muluh T, Wang Y. Combination of CAR T cell therapy and radiotherapy: Opportunities and challenges in solid tumors. Oncology Letters, 2023, 26(1): 1-10.

Marcus D, Ritsaert Lieverse, Klein C, et al. Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy. Cancers, 2021, 13(6): 1468-1468.

DeSelm C, Palomba ML, Yahalom J, et al. Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape. Molecular Therapy, 2018, 26(11): 2542-2552.

Yang CY, Fan M, Miao CH, et al. Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer. Molecular Therapy - Oncolytics, 2020, 17: 571-585.

Liu L, Huang X, Shi F, et al. Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy. Journal of Experimental & Clinical Cancer Research: CR, 2022, 41(1): 56.

Timmer FEF, Geboers B, Nieuwenhuizen S, et al. Pancreatic Cancer and Immunotherapy: A Clinical Overview. Cancers, 2021, 13(16): 4138.

Marofi F, Motavalli R, Safonov VA, et al. CAR T cells in solid tumors: challenges and opportunities. Stem Cell Research & Therapy, 2021, 12(1): 1-16.

Rezaei R, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, et al. Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy. Cancer Gene Therapy, 2021, 29(6): 647-660.

Watanabe K, Luo Y, Da T, et al. Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses. JCI Insight, 2018, 3(7): e99573

Downloads

Published

29-12-2023

How to Cite

Xing, Y. (2023). CAR T-Cell-Based Combination Therapy for Pancreatic Ductal Adenocarcinoma (PDAC). Highlights in Science, Engineering and Technology, 74, 194-201. https://doi.org/10.54097/q7777040