Personalized Dendritic Cell Vaccines—Recent Breakthroughs and Encouraging Clinical Results

Abstract

With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate and adaptive immune system, and have critical roles in the induction of antitumor immunity. However, despite proven immunogenicity and favorable safety profiles, DC-based immunotherapies have not succeeded at inducing significant objective clinical responses. Emerging data suggest that the combination of DC-based vaccination with other cancer therapies may fully unleash the potential of DC-based cancer vaccines and improve patient survival. In this review, we discuss the recent efforts to develop innovative personalized DC-based vaccines and their use in combined therapies, with a particular focus on ovarian cancer and the promising results of mutanome-based personalized immunotherapies.

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

“…These digest the extracellular matrix, aiding tumour invasion and inhibit secretion of IL-12, preventing Th1 T cell differentiation and NK cell activation and, hence, a high level of MMP2 is associated with a poor prognosis. Therefore, recent research into DC vaccines has been aimed at improving DC activation and promoting of T cell function, as well as the use of adjuvant treatments alongside DC vaccines to counteract the effect of an immunosuppressive TME [127].…”

“…Cancers 2020, 12, x 14 of 38 differentiation and NK cell activation and, hence, a high level of MMP2 is associated with a poor prognosis. Therefore, recent research into DC vaccines has been aimed at improving DC activation and promoting of T cell function, as well as the use of adjuvant treatments alongside DC vaccines to counteract the effect of an immunosuppressive TME [127]. The most recent clinical trials surrounding DC vaccines focus on improving the ex vivo steps required to make the vaccine in order to increase efficiency [128].…”

Trained Immunity for Personalized Cancer Immunotherapy: Current Knowledge and Future Opportunities

“…There are several types of DC-vaccines, being the most frequently used the reinfusion of ex vivo derived DC pulsed with tumor-associated antigens (TAAs) or tumor cell lysates and stimulated with TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) (Lee et al, 2002;Koski et al, 2008;Anguille et al, 2014). The DC-based immunotherapy efficiency may be enhanced using immune checkpoint inhibitors, such as anti PD-1 or anti-CTLA-4 antibodies (Mastelic-Gavillet et al, 2019). Carreno and colleges described the vaccination of three stage III resected melanoma patients who received mature autologous DCs pulsed with peptides derived from mutated antigens, with a previous treatment with CTLA-4 blockade.…”

Ribonucleic Acid Engineering of Dendritic Cells for Therapeutic Vaccination: Ready ‘N Able to Improve Clinical Outcome?

“…A drawback, however, is that CD25 is also upregulated on other T cells upon activation, explaining why the recombinant IL-2 diphtheria toxin conjugate only led to increased T-cell stimulation when it was omitted during priming [118]. These days, much more interest goes out to blockade of the potent immune checkpoint inhibitors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligands PD-L1/2, which has already demonstrated remarkable clinical efficacy in different cancers as monotherapy and is increasingly being combined with DC vaccination [119]. One clinical trial by Wilgenhof et al combined ipilimumab (an anti-CTLA-4 antibody) with melanoma-associated antigen RNA-loaded DC vaccination thus far [78].…”