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There is growing interest in immunotherapy for malignant gliomas. This interest stems from a number of immunological observations, together with the failure of conventional therapeutic agents to produce broad and clinically meaningful improvements in survival and quality of life. The challenges faced in translating laboratory-based immunological observations to Phase I and II clinical trials for immunotherapy of gliomas are substantial. Nevertheless, as our understanding of the effects of active specific vaccination in glioma patients grows, results support optimism that such methods may eventually prove useful as an adjunctive treatment for these cancers. This paper highlights a number of barriers encountered in the translational development of a survivin-targeted peptide vaccine (SurVaxM) for patients with malignant gliomas.

The field of cancer therapy has undergone a major transformation in less than a decade due to the introduction of checkpoint inhibitors, the advent of next generation sequencing and the discovery of neoantigens. The key observation that the breadth of each patient's immune response to the unique mutations or neoantigens present in their tumor is directly related to their survival has led oncologists to focus on driving immune responses to neoantigens through vaccination. Oncology has entered the era of precision immunotherapy, and cancer vaccine development is undergoing a paradigm shift. Neoantigens are short peptide sequences found in tumors, but not noncancerous tissues, the vast majority of which are unique to each patient. In addition to providing a description of the distinguishing features of neoantigen discovery platforms, this review will address cross-cutting personalized cancer vaccine design themes and developmental stumbling blocks. Immunoinformatic pipelines that can rapidly scan cancer genomes and identify 'the best' neoantigens are in high demand. Despite the need for such tools, immunoinformatic methods for identifying neoepitopes in cancer genomes are diverse and have not been well-validated. Validation of 'personalized vaccine design pipelines' will bring about a revolution in neoantigen-based vaccine design and delivery. [ABSTRACT FROM AUTHOR]

Introduction: From its earliest days, the US. military has embraced the use of vaccines to fight infectious diseases. The Army Liposome Formulation (ALF) has been a pivotal innovation as a vaccine adjuvant that provides excellent safety and potency and could lead to dual-use military and civilian benefits. For protection of personnel against difficult disease threats found in many areas of the world, Army vaccine scientists have created novel liposome-based vaccine adjuvants. Areas covered: ALF consists of liposomes containing saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA) as an immunostimulant. ALF exhibited safety and strong potency in many vaccine clinical trials. Improvements based on ALF include: ALF adsorbed to aluminum hydroxide (ALFA); ALF containing QS21 saponin (ALFQ); and ALFQ adsorbed to aluminum hydroxide (ALFQA). Preclinical safety and efficacy studies with ALF, LFA, ALFQ, and ALFQA are discussed in preparation for upcoming vaccine trials targeting malaria, HIV-1, bacterial diarrhea, and opioid addiction. Expert opinion: The introduction of ALF in the 1980s stimulated commercial interest in vaccines to infectious diseases, and therapeutic vaccines to cancer, and Alzheimer's disease. It is likely that ALF, ALFA, and ALFQ, will provide momentum for new types of modern vaccines with improved efficacy and safety. [ABSTRACT FROM AUTHOR]

Introduction: Although much progress has been made in the last decade(s) toward development of effective cancer vaccines, there are still important obstacles to therapeutic successes. New generations of cancer vaccines will benefit from a combination adjuvant approach that targets multiple branches of the immune response. Areas covered: Herein we describe how combinatorial adjuvant strategies can help overcome important obstacles to cancer vaccine development, including antigen immunogenicity and tumor immune suppression. Tumor antigens may be both tolerogenic and may utilize active mechanisms to suppress host immunity, including downregulation of MHC molecules to evade recognition and upregulation of immune inhibitory receptors, to subvert an effective immune response. The current cancer vaccine literature was surveyed to identify advancements in the understanding of the biological mechanisms underlying poor antigen immunogenicity and tumor immune evasion, as well as adjuvant strategies designed to overcome them. Expert commentary: Poor immunogenicity of tumor antigens and tumor immune evasion mechanisms make the design of cancer vaccines challenging. Growing understanding of the tumor microenvironment and associated immune responses indicate the importance of augmenting not only the effector response, but also overcoming the endogenous regulatory response and tumor evasion mechanisms. Therefore, new vaccines will benefit from multi-adjuvanted approaches that simultaneously stimulate immunity while preventing inhibition. [ABSTRACT FROM PUBLISHER]

We propose that optimized control of adult-onset cancers requires the incorporation of a defense-based strategy in the form of preemptive immunity induced in healthy cancer-free subjects prior to the appearance of tumors. However, development of such prophylactic immunity has traditionally targeted etiopathogenic agents. We propose that in the absence of available cancer-inducing pathogens, safe and effective protection against the emergence of tumors may be achieved by inducing targeted immunity against tissue-specific self-proteins that are 'retired' from expression at immunogenic levels in normal tissues due to the normal aging process, but are expressed in emerging tumors. Thus, 'retired' self-proteins may substitute for unavailable pathogens as targets for developing prophylactic immunity against tumors we confront with age like breast, ovarian and prostate cancer. Our current efforts involve testing this primary 'immunoprevention' strategy in clinical trials focused on prevention of the more aggressive and lethal forms of breast cancer. [ABSTRACT FROM AUTHOR]

Tumor associated antigen (TAA)-based therapeutic vaccines have great potential as a safe, practical, and cost-efficient alternative to standard treatments for cancer. Clinical efficacy of TAA-based vaccines, however, has yet to be realized and will require adjuvants with pleiotropic functions on immune cells. Such adjuvants need not only to generate/boost T cell responses, but also reverse intrinsic/extrinsic tumor immune evasion mechanisms for therapeutic efficacy. This review focuses on a novel agonistic ligand, SA-4-1BBL, for 4-1BB costimulatory receptor as an adjuvant of choice because of its ability to: i) serve as a vehicle to deliver TAAs to dendritic cells (DCs) for antigen uptake and cross-presentation to CD8+ T cells; ii) augment adaptive Th1 and innate immune responses; and iii) overcome various immune evasion mechanisms, cumulatively translating into therapeutic efficacy in preclinical tumor models. [ABSTRACT FROM AUTHOR]

Based on lessons learned with various immune interventions, this review aims to provide a constructive framework for repositioning therapeutic cancer vaccination. Intensive research throughout the past decade has identified key hurdles interfering with the efficacy of cancer vaccines. The vaccination concept still holds promise if positioned appropriately in minimal residual disease and select early disease stage cancer indications. However, in advanced cancer, it must be integrated with complementary immune interventions to ensure reconstruction of a functional immune repertoire and simultaneous blockade of immune inhibiting mechanisms. Vaccination could render complex and integrative immune interventions simpler, safer and more effective. The near future will witness an explosion of activities in the cancer immunotherapy arena, witnessing a rational repositioning of vaccines rather than their extinction. [ABSTRACT FROM AUTHOR]

Effective delivery of tumor antigens to APCs is one of the key steps for eliciting a strong and durable immune response to tumors. Several cancer vaccines have been evaluated in clinical trials, based on soluble peptides, but results have not been fully satisfactory. To improve immunogenicity particles provide a valid strategy to display and/or incorporate epitopes which can be efficiently targeted to APCs for effective induction of adaptive immunity. In the present review, we report some leading technologies for developing particulate vaccines employed in cancer immunotherapy, highlighting the key parameters for a rational design to elicit both humoral and cellular responses. [ABSTRACT FROM AUTHOR]