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The emergence of immunotherapy for the treatment of human cancers has heralded a new era in oncology, one that is making its way into the veterinary clinic. As the immune system of many animal species commonly seen by veterinarians is similar to humans, there is great hope for the translation of human therapies into veterinary oncology. The simplest approach for veterinarians would be to adopt existing reagents that have been developed for human medicine, due to the potential of reduced cost and the time it takes to develop a new drug. However, this strategy may not always prove to be effective and safe with regard to certain drug platforms. Here, we review current therapeutic strategies that could exploit human reagents in veterinary medicine and also those therapies which may prove detrimental when human-specific biological molecules are used in veterinary oncology. In keeping with a One Health framework, we also discuss the potential use of single-domain antibodies (sdAbs) derived from camelid species (also known as Nanobodies™) for therapies targeting multiple veterinary animal patients without the need for species-specific reformulation. Such reagents would not only benefit the health of our veterinary species but could also guide human medicine by studying the effects of outbred animals that develop spontaneous tumors, a more relevant model of human diseases compared to traditional laboratory rodent models.

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator-boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod-modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti-tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor-draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor-bearing mice. The combination of OR@Lac and ibrutinib, a myeloid-derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor-bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs., (© 2024 Wiley‐VCH GmbH.)

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membranes and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, the authors delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Last, the challenges and trends in this field are discussed. This comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines., (© 2024 Wiley‐VCH GmbH.)

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Hepatocellular carcinoma is one of the most common malignancies globally. It not only has a hidden onset but also progresses rapidly. Most HCC patients are already in the advanced stage of cancer when they are diagnosed, and have even lost the opportunity for surgical treatment. As an inflammation-related tumor, the immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy can activate tumor-specific immune responses, which brings a new hope for the treatment of HCC. At the present time, main immunotherapy strategies of HCC include immune checkpoint inhibitors, tumor vaccines, adoptive cell therapy, and so on. This article reviews the application and research progress of immune checkpoint inhibitors, tumor vaccines, and adoptive cell therapy in the treatment of HCC.

Hepatocellular carcinoma is one of the most common malignancies globally. It not only has a hidden onset but also progresses rapidly. Most HCC patients are already in the advanced stage of cancer when they are diagnosed, and have even lost the opportunity for surgical treatment. As an inflammation-related tumor, the immunosuppressive microenvironment of HCC can promote immune tolerance through a variety of mechanisms. Immunotherapy can activate tumor-specific immune responses, which brings a new hope for the treatment of HCC. At the present time, main immunotherapy strategies of HCC include immune checkpoint inhibitors, tumor vaccines, adoptive cell therapy, and so on. This article reviews the application and research progress of immune checkpoint inhibitors, tumor vaccines, and adoptive cell therapy in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Tumor vaccines aim to expand tumor-specific T cells and reactivate existing tumor-specific T cells that are in a dormant or unresponsive state. As such, there is growing interest in improving the durable anti-tumor activity of tumor vaccines. Failure of vaccine-activated T cells to protect against tumors is thought to be the result of the immune escape mechanisms of tumor cells and the intricate immunosuppressive tumor microenvironment. In this review, we discuss how tumor cells and the tumor microenvironment influence the effects of tumor infiltrating lymphocytes and summarize how to improve the efficacy of tumor vaccines by improving the design of current tumor vaccines and combining tumor vaccines with other therapies, such as metabolic therapy, immune checkpoint blockade immunotherapy and epigenetic therapy.

Urothelial cancer (UC) is one of the leading onco-urological diseases. The lack of clinical manifestations of the disease at earlier stages does not allow assigning an adequate therapy in good time. Currently they extensively use conventional methods of treatment, which are constantly improving. Nevertheless, such methods are not always sufficiently effective: they neither always avert recurring, nor ensure sufficient remission and longevity of a patient. Identification of new trends in the early diagnostics of not only cancers but also pre-cancers plays an important role in forming conceptually new approaches to medical treatments. Molecular genetic features of UC have shown a significant chromosomal mutational variability, the dependence of genetic variations on the tumor invasion level, as well as its high level of immunizing power. Successes achieved in understanding the processes taking place not only in the tumor microenvironment but also in tumors have enabled creating fundamentally new anticancer drugs and achieving a significant progress in treating UC. This article presents a new classification of UCs based on immune histochemical data and molecular genetic characteristics of tumors, presents a cluster analysis of various types of UCs, recites present-day data on the disease incidence, analyses up-to-date conventional and innovative methods of UC treatment including non-specific and specific immunotherapy, describes the underlying mechanisms preventing tumors to evade immune surveillance, shows the role of immune checkpoints and their inhibitors, target and cytokine therapies, tumor vaccines, cell-based therapies, combined and integral methods of noninvasive and metastatic UC, as well as describes the results of clinical trials when using various methods of tumor treatments.

Tumor vaccines aim to expand tumor-specific T cells and reactivate existing tumor-specific T cells that are in a dormant or unresponsive state. As such, there is growing interest in improving the durable anti-tumor activity of tumor vaccines. Failure of vaccine-activated T cells to protect against tumors is thought to be the result of the immune escape mechanisms of tumor cells and the intricate immunosuppressive tumor microenvironment. In this review, we discuss how tumor cells and the tumor microenvironment influence the effects of tumor infiltrating lymphocytes and summarize how to improve the efficacy of tumor vaccines by improving the design of current tumor vaccines and combining tumor vaccines with other therapies, such as metabolic therapy, immune checkpoint blockade immunotherapy and epigenetic therapy. [ABSTRACT FROM AUTHOR]

Abstract Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

Construction of an optimal vaccine against tumors relies on the availability of appropriate tumor-specific antigens capable to stimulate CD4+ T helper cells (TH) and CD8+ cytolytic T cells (CTL). CTL are considered the major effectors of the anti-tumor adaptive immune response as they recognize antigens presented on MHC class I (MHC-I) molecules usually expressed in all cells and thus also in tumors. However, attempts to translate in clinics vaccination protocols based only on tumor-specific MHC-I-bound peptides have resulted in very limited, if any, success. We believe failure was mostly due to inadequate triggering of the TH arm of adaptive immunity, as TH cells are necessary to trigger and maintain the proliferation of all the immune effector cells required to eliminate tumor cells. In this review, we focus on a novel strategy of anti-tumor vaccination established in our laboratory and based on the persistent expression of MHC class II (MHC-II) molecules in tumor cells. MHC-II are the restricting elements of TH recognition. They are usually not expressed in solid tumors. By genetically modifying tumor cells of distinct histological origin with the MHC-II transactivator CIITA, the physiological controller of MHC-II gene expression discovered in our laboratory, stable expression of all MHC class II genes was obtained. This resulted in tumor rejection or strong retardation of tumor growth in vivo in mice, mediated primarily by tumor-specific TH cells as assessed by both depletion and adoptive cell transfer experiments. Importantly these findings led us to apply this methodology to human settings for the purification of MHC-II-bound tumor specific peptides directly from tumor cells, specifically from hepatocarcinomas, and the construction of a multi-peptide (MHC-II and MHC-I specific) immunotherapeutic vaccine. Additionally, our approach unveiled a noticeable exception to the dogma that dendritic cells are the sole professional antigen presenting cells (APC) capable to prime naïve TH cells, because CIITA-dependent MHC-II expressing tumor cells could also perform this function. Thus, our approach has served not only to select the most appropriate tumor specific peptides to activate the key lymphocytes triggering the anti-tumor effector functions but also to increase our knowledge of intimate mechanisms governing basic immunological processes.

Tumor vaccines are an important asset in the field of cancer immunotherapy. Whether prophylactic or therapeutic, these vaccines aim to enhance the T cell-mediated anti-tumor immune response that is orchestrated by dendritic cells. Although promising preclinical and early-stage clinical results have been obtained, large-scale clinical implementation of cancer vaccination is stagnating due to poor clinical response. The challenges of clinical efficacy of tumor vaccines can be mainly attributed to tumor induced immunosuppression and poor immunogenicity of the chosen tumor antigens. Recently, intratumor heterogeneity and the relation with tumor-specific neoantigen clonality were put in the equation.In this perspective we provide an overview of recent studies showing how personalized tumor vaccines containing multiple neoantigens can broaden and enhance the anti-tumor immune response. Furthermore, we summarize advances in the understanding of the intratumor mutational landscape containing different tumor cell subclones and the temporal and spatial diversity of neoantigen presentation and burden, and the relation between these factors with respect to tumor immunogenicity. Together, the presented knowledge calls for the investment in the characterization of neoantigens in the context of intratumor heterogeneity to improve clinical efficacy of personalized tumor vaccines.

Construction of an optimal vaccine against tumors relies on the availability of appropriate tumor-specific antigens capable to stimulate CD4+ T helper cells (TH) and CD8+ cytolytic T cells (CTL). CTL are considered the major effectors of the anti-tumor adaptive immune response as they recognize antigens presented on MHC class I (MHC-I) molecules usually expressed in all cells and thus also in tumors. However, attempts to translate in clinics vaccination protocols based only on tumor-specific MHC-I-bound peptides have resulted in very limited, if any, success. We believe failure was mostly due to inadequate triggering of the TH arm of adaptive immunity, as TH cells are necessary to trigger and maintain the proliferation of all the immune effector cells required to eliminate tumor cells. In this review, we focus on a novel strategy of anti-tumor vaccination established in our laboratory and based on the persistent expression of MHC class II (MHC-II) molecules in tumor cells. MHC-II are the restricting elements of TH recognition. They are usually not expressed in solid tumors. By genetically modifying tumor cells of distinct histological origin with the MHC-II transactivator CIITA, the physiological controller of MHC-II gene expression discovered in our laboratory, stable expression of all MHC class II genes was obtained. This resulted in tumor rejection or strong retardation of tumor growth in vivo in mice, mediated primarily by tumor-specific TH cells as assessed by both depletion and adoptive cell transfer experiments. Importantly these findings led us to apply this methodology to human settings for the purification of MHC-II-bound tumor specific peptides directly from tumor cells, specifically from hepatocarcinomas, and the construction of a multi-peptide (MHC-II and MHC-I specific) immunotherapeutic vaccine. Additionally, our approach unveiled a noticeable exception to the dogma that dendritic cells are the sole professional antigen presenting cells (APC) capable to prime naïve TH cells, because CIITA-dependent MHC-II expressing tumor cells could also perform this function. Thus, our approach has served not only to select the most appropriate tumor specific peptides to activate the key lymphocytes triggering the anti-tumor effector functions but also to increase our knowledge of intimate mechanisms governing basic immunological processes. [ABSTRACT FROM AUTHOR]

Tumor vaccines are an important asset in the field of cancer immunotherapy. Whether prophylactic or therapeutic, these vaccines aim to enhance the T cell-mediated anti-tumor immune response that is orchestrated by dendritic cells. Although promising preclinical and early-stage clinical results have been obtained, large-scale clinical implementation of cancer vaccination is stagnating due to poor clinical response. The challenges of clinical efficacy of tumor vaccines can be mainly attributed to tumor induced immunosuppression and poor immunogenicity of the chosen tumor antigens. Recently, intratumor heterogeneity and the relation with tumor-specific neoantigen clonality were put in the equation.In this perspective we provide an overview of recent studies showing how personalized tumor vaccines containing multiple neoantigens can broaden and enhance the anti-tumor immune response. Furthermore, we summarize advances in the understanding of the intratumor mutational landscape containing different tumor cell subclones and the temporal and spatial diversity of neoantigen presentation and burden, and the relation between these factors with respect to tumor immunogenicity. Together, the presented knowledge calls for the investment in the characterization of neoantigens in the context of intratumor heterogeneity to improve clinical efficacy of personalized tumor vaccines. [ABSTRACT FROM AUTHOR]