Transforming pancreaticobiliary cancer treatment: Exploring the frontiers of adoptive cell therapy and cancer vaccines

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Abstract

Pancreaticobiliary cancer, encompassing malignancies of both the pancreatic and biliary tract, presents a formidable clinical challenge marked by a uniformly bleak prognosis. The asymptomatic nature of its early stages often leads to delayed detection, contributing to an unfavorable 5-year overall survival rate. Conventional treatment modalities have shown limited efficacy, underscoring the urgent need for alternative therapeutic approaches. In recent years, immunotherapy has emerged as a promising avenue in the fight against pancreaticobiliary cancer. Strategies such as therapeutic vaccines and the use of tumor-infiltrating lymphocytes have garnered attention for their potential to elicit more robust and durable responses. This review seeks to illuminate the landscape of emerging immunotherapeutic interventions, offering insights from both clinical and research perspectives. By deepening our understanding of pancreaticobiliary cancer and exploring innovative treatment modalities, we aim to catalyze improvements in patient outcomes and quality of life.

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Abstract

Tai and colleagues describe that pancreaticobiliary cancers present important challenges despite treatment advances. Immunotherapy holds promise, but faces limitations due to tumor microenvironment complexities. Emerging strategies like adoptive cell therapy and cancer vaccines aim to boost T cell activity, potentially improving treatment outcomes for these aggressive cancers.

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Most cited references 120

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Cancer Statistics, 2021

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

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Signatures of mutational processes in human cancer

Ludmil Alexandrov, Serena Nik-Zainal, David Wedge … (2015)

All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.

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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

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Author and article information

Contributors

Lee-Hwa Tai

Journal

Journal ID (nlm-ta): Mol Ther Oncol

Journal ID (iso-abbrev): Mol Ther Oncol

Title: Molecular Therapy Oncology

Publisher: American Society of Gene & Cell Therapy

ISSN (Electronic): 2950-3299

Publication date PMC-release: 08 June 2024

Publication date Collection: 19 September 2024

Publication date (Electronic): 08 June 2024

Volume: 32

Issue: 3

Electronic Location Identifier: 200825

Affiliations

[1 ]Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada

[2 ]Department of Surgery, Division of General Surgery, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada

[3 ]Centre de Recherche du CHUS, Sherbrooke, QC J1H 5N4, Canada

Author notes

[∗ ]Corresponding author: Lee-Hwa Tai, Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada. lee-hwa.tai@ 123456usherbrooke.ca

Article

Publisher Item ID: S2950-3299(24)00067-5 Publisher ID: 200825

DOI: 10.1016/j.omton.2024.200825

PMC ID: 11246060

PubMed ID: 39006944

SO-VID: 7e398e44-b82b-4f5c-b410-f5f3bc51a0e4

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Transforming pancreaticobiliary cancer treatment: Exploring the frontiers of adoptive cell therapy and cancer vaccines

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Vaccines

Most cited references 120

Cancer Statistics, 2021

Signatures of mutational processes in human cancer

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

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