The next wave of cellular immunotherapies in pancreatic cancer

Dannel Yeo; Caroline Giardina; Payal Saxena; John E J Rasko

doi:10.1016/j.omto.2022.01.010

The next wave of cellular immunotherapies in pancreatic cancer

Mol Ther Oncolytics. 2022 Feb 1:24:561-576. doi: 10.1016/j.omto.2022.01.010. eCollection 2022 Mar 17.

Authors

Dannel Yeo^{1

2

3}, Caroline Giardina^{2

4}, Payal Saxena^{2

5}, John E J Rasko^{1

2

3

4}

Affiliations

¹ Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW 2050, Australia.
² Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia.
³ Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW 2050, Australia.
⁴ Gene and Stem Cell Therapy Program, Centenary Institute, The University of Sydney, Camperdown, NSW 2050, Australia.
⁵ Division of Gastroenterology, Department of Medicine, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW 2050, Australia.

Abstract

Pancreatic cancer is an aggressive disease that is predicted to become the second leading cause of cancer-related death worldwide by 2030. The overall 5-year survival rate is around 10%. Pancreatic cancer typically presents late with locally advanced or metastatic disease, and there are limited effective treatments available. Cellular immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has had significant success in treating hematological malignancies. However, CAR T cell therapy efficacy in pancreatic cancer has been limited. This review provides an overview of current and ongoing CAR T cell clinical studies of pancreatic cancer and the major challenges and strategies to improve CAR T cell efficacy. These strategies include arming CAR T cells; developing off-the-shelf allogeneic CAR T cells; using other immune CAR cells, like natural killer cells and tumor-infiltrating lymphocytes; and combination therapy. Careful incorporation of preclinical models will enhance management of affected individuals, assisting incorporation of cellular immunotherapies. A multifaceted, personalized approach involving cellular immunotherapy treatment is required to improve pancreatic cancer outcomes.

Keywords: CAR T cell therapy; adoptive T cell therapy; cellular immunotherapy; checkpoint blockade; combination therapy; organoids; pancreatic cancer; preclinical models; tumor microenvironment.

Publication types

Review