Pancreatic cancer, with the prevalent form being pancreatic ductal adenocarcinoma (PDAC), accounts for more than 90% of pancreatic cancer cases (Miller et al., 2016). This disease is characterized by its aggressive and often fatal nature, attributed to the absence of reliable biomarkers, therapy resistance, high recurrence rates post-surgery, and high metastasis characteristics (Wang et al., 2021). It has one of the lowest survival rate and is projected to become the second leading cause of cancer-related deaths worldwide (Kamisawa et al., 2016; Rahib et al., 2021). Understanding the molecular pathology of PDAC remains a complex challenge, further complicating its management. Traditional treatments like chemotherapy, surgery, and radiation have not shown significant improvements in outcomes (Sarantis et al., 2020). While surgical resection and chemotherapy have improved survival for early-stage cancer cases, their impact diminishes for late-stage disease (Li et al., 2022). The World Health Organization classifies PDAC into nine histological subtypes, including, colloid carcinoma, signet ring cell carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, micropapillary carcinoma, adenosquamous carcinoma, hepatoid carcinoma, undifferentiated carcinoma, medullary carcinoma, and undifferentiated carcinoma with rhabdoid cells (Taherian et al., 2022). In-depth insights into PDAC pathology are described elsewhere (Haeberle and Esposito, 2019; Taherian et al., 2022). Various other pancreatic tumors include benign tumor (such as serous cystadenoma, pyloric gland adenoma, acinar cell cystadenoma), neuroendocrine neoplasms (like gastrinoma, neuroendocrine carcinoma, pancreatic neuroendocrine microadenoma), and malignant tumors (including acinar cell carcinoma, acinar cell cystadenocarcinoma, pancreatoblastoma) (Yadav et al., 2021).

Resistance to conventional chemotherapy in the context of PDAC is primarily due to the presence of the extracellular matrix (ECM) and fibrosis within the tumor microenvironment, commonly referred as Desmoplasia (Barriga et al., 2019; Kuol et al., 2017). Even radiation therapy struggles to overcome these challenges in achieving targeted cytotoxicity. The hope for the management of the disease lies in immunotherapy (Yoon et al., 2021). Immunotherapy offers a promising avenue, with several potential targets such as programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), T cells (chimeric antigen receptor T cells (CAR-T cells)), etc. (Cho et al., 2017; Yoon et al., 2021), being investigated for their therapeutic potential. The molecular pathology is outlined in Fig. 1.

In addition, a novel approach to managing the disease involves preventive measures through vaccination. Herein, we focus on ongoing development of immunotherapy, in particular the use of monoclonal antibodies (mAbs) for the treatment of PDAC, providing a detailed overview of the clinical trials currently in progress.