Dendritic cell vaccine therapy for colorectal cancer

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States despite an array of available treatment options. Current standard-of-care interventions for this malignancy include surgical resection, chemotherapy, and targeted therapies depending on the disease stage. Specifically, infusion of anti-vascular endothelial growth factor agents in combination with chemotherapy was an important development in improving the survival of patients with advanced colorectal cancer, while also helping give rise to other forms of anti-angiogenic therapies. Yet, one approach by which tumor angiogenesis may be further disrupted is through the administration of a dendritic cell (DC) vaccine targeting tumor-derived blood vessels, leading to cytotoxic immune responses that decrease tumor growth and synergize with other systemic therapies. Early generations of such vaccines exhibited protection against various forms of cancer in pre-clinical models, but clinical results have historically been disappointing. Sipuleucel-T (Provenge®) was the first, and to-date, only dendritic cell-based therapy to receive FDA approval after significantly increasing overall survival in prostate cancer patients. The unparalleled success of Sipuleucel-T has helped revitalize the clinical development of dendritic cell vaccines, which will be examined in this review. We also highlight the promise of these vaccines to instill anti-angiogenic immunity for individuals with advanced colorectal cancer.

Keywords: Axitinib (6450551); Cyclophosphamide (2907); Cytotoxic chemotherapy; Dasatinib (3062316); Doxorubicin (31703); Fluorouracil (3385); Immunotherapy; Listeria monocytogenes; Oxaliplatin (43805); Regorafenib (11167602); Sipuleucel-T; Sunitinib (5329102); Targeted cancer therapy; Tumor angiogenesis.

Figure 1.

General overview of directing dendritic cell vaccines against colorectal cancer-derived blood vessels. Abbreviation used: dendritic cell (DC). Created with Biorender.com.

Figure 2.

Standard ex vivo approach for generating dendritic cell vaccines for patient infusion. Abbreviation used: dendritic cell (DC). Created with Biorender.com.