1,721,170 research outputs found
Immune response to tumor
No full textThe immune system of the host responds to tumor growth as it does to infectious agents, with specific (e.g., Tcells and antibodies) and nonspecific (e.g., natural killer cells and cytokines) effector and regulatory mechanisms. The immune response reduces the number of tumors arising in the host, but is no longer effective against established tumors. Tumor immunotherapy is the attempt to elicit a therapeutic immune response in cancer patients
Vaccines for cancer prevention and treatment
No full textThe advent of vaccines heralded significant advancements in public health, with the successful eradication of smallpox and rinderpest – a zoonotic disease which caused devastating livestock losses - and the prevention of many other potentially severe infectious diseases like polio and measles. In the field of oncology, the development and implementation of vaccines against hepatitis B virus (HBV) and human papillomaviruses (HPV) have substantially reduced the incidence of liver and cervical cancers. The remarkable success of HPV vaccination campaigns suggests that we may be on the verge of witnessing the eradication of cervical cancer, much as vaccines have previously eradicated smallpox, at least in those countries that record full population compliance with vaccination programs.
While the success of HBV and HPV vaccines highlights the efficacy of targeting virus-induced cancers, there is a growing impetus to expand vaccine development to address other cancer-related pathogens and even non-infectious tumors. This special issue of Molecular Aspects of Medicine focuses on the innovative and transformative potential of vaccines for cancer prevention and therapy. The reviews in this issue cover a broad spectrum of topics, including basic concepts in this research field, such as the various level of preventive interventions, the types of targetable antigens, the various platforms and formulations of anti-cancer vaccines, the appropriateness of pre-clinical models, and the contribution of comparative oncology. Moreover, further clinical aspects are treated, including the promise of cancer susceptibility syndromes as ideal candidates for anti-cancer vaccination, the advancements in vaccination against breast cancer, the potential of targeting other cancer-related microbes, and much more
Immunoprevention
No full textImmunoprevention
Definition
Prevention of cancer onset or of early cancer development and progression by means of immunological
treatments, such as vaccines, antibodies, or cytokines.
Characteristics
Immunoprevention of cancer can be applied to tumors caused by viruses and other infectious agents or to
tumors unrelated to infectious agents. In both cases, the aim is the same; however, the underlying concepts
and the advancement of clinical development are different. Prevention of viral tumors is based on vaccines
against viral antigens, whereas immunoprevention of tumors unrelated to infectious agents targets
antigens expressed by early neoplastic cells
Virus-like antigen display for cancer vaccine development, what is the potential?
No full textVaccines containing whole viruses induce strong, protective humoral and cellular immune responses, whereas vaccines based on soluble proteins have generally shown poor efficacy. Virus-like particles (VLP) assembled from a single virus protein allow the display of a closely spaced, repetitive epitope pattern that mimics that of infectious agents and provide optimal stimulation of the mammalian immune system. However, the correct assembly of VLPs with large and complex proteins is challenging. The development of a simple modular system, based on highly reactive split-protein tag/catcher binding partners, enabled the high-density display of large proteins on the surface of non-enveloped icosahedral VLPs of bacteriophage origin. This versatile technology was used to develop a VLP vaccine displaying the whole extracellular domain of the human oncogene HER-2. In transgenic mice expressing human HER-2, the VLP vaccine induced strong antibody responses that protected the mice from the onset and growth of mammary carcinomas and inhibited in vitro human cell lines sensitive and resistant to the therapeutic monoclonal antibody trastuzumab. Such vaccines hold promise for integration in therapeutic regimes of breast cancer and other HER-2-positive human tumors
The Promise of Preventive Cancer Vaccines
Full text linkYears of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future
Cancer immunoprevention: from mice to early clinical trials
Full text linkAbstract Cancer immunoprevention is based on the fact that a functioning immune system controls tumor onset and development in humans and animals, thus leading to the idea that the enhancement of immune responses in healthy individuals could effectively reduce cancer risk later in life. Successful primary immunoprevention of tumors caused by hepatitis B and papilloma viruses is already implemented at the population level with specific vaccines. The immunoprevention of human tumors unrelated to infectious agents is an outstanding challenge. Proof-of-principle preclinical studies in genetically-modified or in carcinogen-exposed mice clearly demonstrated that vaccines and other immunological treatments induce host immune responses that effectively control tumor onset and progression, eventually resulting in cancer prevention. While a straightforward translation to healthy humans is currently unfeasible, a number of pioneering clinical trials showed that cancer immunoprevention can be effectively implemented in human cohorts affected by specific cancer risks, such as preneoplastic/early neoplastic lesions. Future developments will see the implementation of cancer immunoprevention in a wider range of conditions at risk of tumor development, such as the exposure to known carcinogens and genetic predispositions
Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma
Full text linkAbstract: Osteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting
bone. It is characterized by a complex genotype, mainly due to the high frequency of chromothripsis, which leads to multiple somatic copy number alterations and structural rearrangements. Any
effort to design genome-driven therapies must therefore consider such high inter- and intra-tumor
heterogeneity. Therefore, many laboratories and international networks are developing and sharing
OS patient-derived xenografts (OS PDX) to broaden the availability of models that reproduce OS
complex clinical heterogeneity. OS PDXs, and new cell lines derived from PDXs, faithfully preserve
tumor heterogeneity, genetic, and epigenetic features and are thus valuable tools for predicting drug
responses. Here, we review recent achievements concerning OS PDXs, summarizing the methods
used to obtain ectopic and orthotopic xenografts and to fully characterize these models. The availability of OS PDXs across the many international PDX platforms and their possible use in PDX clinical trials are also described. We recommend the coupling of next-generation sequencing (NGS) data
analysis with functional studies in OS PDXs, as well as the setup of OS PDX clinical trials and coclinical trials, to enhance the predictive power of experimental evidence and to accelerate the clinical
translation of effective genome-guided therapies for this aggressive disease
Bioprofiling TS/A Murine Mammary Cancer for a Functional Precision Experimental Model
Full text linkThe TS/A cell line was established in 1983 from a spontaneous mammary tumor arisen in an inbred BALB/c female mouse. Its features (heterogeneity, low immunogenicity and metastatic ability) rendered the TS/A cell line suitable as a preclinical model for studies on tumor-host interactions and for gene therapy approaches. The integrated biological profile of TS/A resulting from the review of the literature could be a path towards the description of a precision experimental model of mammary cancer
Preclinical vaccines against mammary carcinoma.
Full text linkVaccines against human breast cancer are an unfulfilled promise. Despite decades of
promising preclinical and clinical research, no vaccine is currently available for breast cancer
patients. Preclinical research has much to do with this failure, as early mouse models of
mammary carcinoma did not mirror the molecular, cellular, antigenic and immunological
features of human breast cancer. The advent of HER-2 transgenic mice gave impulse to a
new generation of cell and DNA vaccines against mammary carcinoma, that in turn led to
the definition of significant antigenic (oncoantigens) and cellular (cancer-initiating cells,
preneoplastic lesions, incipient metastases) targets. Future preclinical developments will
include the discovery of novel oncoantigens in HER-2-negative mammary carcinoma and the
targeting of activated HER-2 molecular variants. Translation to clinically effective vaccines will
be fostered not only by new preclinical model systems, but also by the possibility to conduct
veterinary vaccination trials in companion animals
HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy
Full text linkRhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features
allow for distinction between subtypes: morphology and presence/absence of a translocation between
the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar
RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of
receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is
comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting
of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases
contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell
growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation
with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a
role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy.
HER family members could be exploited for therapeutic approaches in two ways: blocking the
HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting
expressed HER members to vehiculate toxins or immune effectors
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