Optimizing dendritic cell-based approaches for cancer immunotherapy (original) (raw)

Dendritic Cell-Based Vaccination in Cancer: Therapeutic Implications Emerging from Murine Models

Frontiers in Immunology, 2015

Dendritic cells (DCs) play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel-T), there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts toward an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models...

Integrating Next-Generation Dendritic Cell Vaccines into the Current Cancer Immunotherapy Landscape

Trends in immunology, 2017

Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy. In addition, using existing data we compare DC vaccines with ICIs targeting CTLA4, PD1, and PD-L1, and argue that in various contexts next-generation DC vaccines are ready to meet some challenges currently confronting ICIs, thereby raising the need to integrate DC vaccines in future combinatorial immunotherapy regimens.

Dendritic Cell Based Cancer Therapy

2012

Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DCbased anticancer vaccines are capable of activating tumorspecific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DCbased therapeutic vaccine (sipuleucel-T, Provenge ®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond

Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications

Frontiers in Cell and Developmental Biology, 2021

Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions. They have proven to potentially take up and process tumor-associated antigens (TAAs). In this regard, researchers have developed strategies such as genetically engineered or TAA-pulsed DC vaccines; these manipulated DCs have shown significant outcomes in clinical and preclinical models. Here, we review DC classification and address how DCs are skewed into an immunosuppressive phenotype in cancer patients. Additionally, we present the advancements in DCs as a platform for cancer immunotherapy, emphasizing the technologies used for in vivo targeting of endogenous DCs, ex vivo generated vaccines from peripheral blood monocytes, and induced pluripotent stem cell-derived DCs (iPSC-DCs) to boost antitumoral immunity.

Trial watch: Dendritic cell-based interventions for cancer therapy

Oncoimmunology, 2012

Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, ...

Current State and Perspectives of Dendritic Cell Vaccination in Cancer Immunotherapy

Skin Pharmacology and Physiology, 2006

Recent progress in the approach towards immunotherapy of cancer consists in molecular defi nition of tumor antigens, new tools for phenotypical and functional characterization of tumor-specifi c effector cells and clinical use of novel adjuvants for optimal stimulation of a cancer-specifi c immune response such as dendritic cells. In spite of these advances and immunological as well as clinical responses in selected patients, mechanisms involved in dendritic-cell-based cancer immunotherapy are still poorly understood. Therefore, a standardized study design and small pilot trials are needed to explore open scientifi c questions in future clinical trials. This review focuses on the different parameters of dendritic cell biology relevant to cancer immunotherapy and on innovative approaches to hopefully enhance the effi cacy of dendritic cell vaccination.

Dendritic cell-based therapeutic cancer vaccines: what we have and what we need

Future Oncology, 2009

Therapeutic cancer vaccines rely on the immune system to eliminate tumor cells. In contrast to chemotherapy or passive (adoptive) immunotherapies with antibodies or ex vivo-expanded T cells, therapeutic vaccines do not have a direct anti-tumor activity, but aim to reset patients’ immune systems to achieve this goal. Recent identification of effective ways of enhancing immunogenicity of tumor-associated antigens, including the use of dendritic cells and other potent vectors of cancer vaccines, provide effective tools to induce high numbers of circulating tumor-specific T cells. However, despite indications that some of the new cancer vaccines may be able to delay tumor recurrence or prolong the survival of cancer patients, their ability to induce cancer regression remains low. Recent reports help to identify and prospectively remove the remaining obstacles towards effective therapeutic vaccination of cancer patients. They indicate that the successful induction of tumor-specific T cel...

Dendritic cells and cancer immunotherapy

Current Opinion in Immunology, 2014

Dendritic cells (DC) play an essential role in the induction and regulation of immune responses, including the generation of cytotoxic T lymphocytes (CTL) for the eradication of cancers. DC-based cancer vaccines are well tolerated with few side effects and can generate anti-tumour immune responses, but overall they have been of limited benefit. Recent studies have demonstrated that CD141(+) DC play an important role in anti-tumour responses. These are now attractive targets for the development of vaccines that directly target DC in vivo. An understanding of the functional specialisations of DC subsets, strategies for the delivery of tumour Ag to DC and for enhancing immune responses, point to promising new avenues for the design of more effective DC-based cancer vaccines.

Towards the rational design of a next-generation dendritic cell vaccine for cancer immunotherapy

Cell and Gene Therapy Insights, 2021

As professional antigen presenting cells (APCs) capable of eliciting primary immune responses among naïve T cells, dendritic cells (DCs) offer an attractive target for immune intervention. While some strategies for vaccination have sought to deliver antigens direct to DCs in vivo, others have pulsed DCs with target antigens ex vivo prior to administration. Indeed, numerous clinical studies of cancer immunotherapy have been conducted over the past two decades based on this approach, most of them benefitting from the ease with which DCs may be differentiated in vitro from the peripheral blood monocytes of individual patients. Nevertheless, while therapies exploiting monocyte-derived DCs (moDCs) have been shown to be safe, clinical outcomes have been disappointing, efficacy having been limited by factors including the type of DCs used and the source of tumor antigens. Here we review recent developments in identifying DC subsets with more favorable properties for use in cancer vaccination, with particular emphasis on CD141 + DCs capable of antigen cross-presentation and discuss alternative sources, such as induced pluripotent stem cells (iPSCs), amenable to manufacture at scale. Furthermore, we assess how different sources of tumor antigens may complement this approach for the design of next generation DC vaccines.