Vaccines, Adjuvants, and Dendritic Cell Activators--Current Status and Future Challenges

Abstract

Cancer vaccines offer a low-toxicity approach to induce anticancer immune responses. They have shown promise for clinical benefit with one cancer vaccine approved in the United States for advanced prostate cancer. As other immune therapies are now clearly effective for treatment of advanced cancers of many histologies, there is renewed enthusiasm for optimizing cancer vaccines for use to prevent recurrence in early-stage cancers and/or to combine with other immune therapies for therapy of advanced cancers. Future advancements in vaccine therapy will involve the identification and selection of effective antigen formulations, optimization of adjuvants, dendritic cell (DC) activation, and combination therapies. In this summary we present the current practice, the broad collection of challenges, and the promising future directions of vaccine therapy for cancer.

Figure 1

Cancer vaccine trials listed as open at ClinicalTrials.gov September 2014. The number of trials for each cancer type are shown in the bar graph. The number with each type of antigen presentation is shown in the inset table. RCC = renal cell carcinoma; CRC = colorectal cancer; HNSCC = head and neck squamous cell carcinoma.

Figure 2

Types of cancer antigens, with examples for each.

Figure 3

Adjuvants being used in clinical trials of cancer vaccines. Cancer vaccine trials listed as open at Clinical Trials.gov (Sept 2014) were assessed for the adjuvants used, showing the number of trials with each A) local and B) systemic vaccine adjuvants. IFA = incomplete Freund’s adjuvant; IL-12 = interleukin-12; CD40L = CD40 ligand; Cy = cyclophosphamide; IDOi = indoleamine-2,3-dis=oxygenase inhibitor; CT-011 and nivolumab are PD-1 antibodies.

Figure 4

Cancer vaccines commonly employ agents that induce “danger” by mimicking foreign pathogens.