The Roles of the Virome in Cancer

Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces—which contain mainly bacteria and their viruses (phages)—from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.

Therapeutic Potential of Cancer Vaccine Based on MHC Class I Cryptic Peptides Derived from Non-Coding Regions

MHC class I molecules display intracellular peptides on cell surfaces to enable immune surveillance under pathological conditions. The source of MHC class I antigens responsible for cancer protection is not fully understood. Here, we explored the MHC class I peptidome in mouse colon cancer cells using a proteogenomic approach. We showed that cryptic peptides derived from unconventional short open reading frames accounted for part of the MHC class I peptidome. Moreover, cancer growth was significantly prevented in mice immunized with a cocktail of synthesized cryptic peptides. Together, our data showed that the source of cancer antigens was not limited to fragments of consensus proteins. Cryptic antigens were displayed by MHC molecules and mediated anti-cancer effects, suggesting their therapeutic potential for cancer prevention.

The Roles of the Virome in Cancer

Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces – which contains mainly bacteria and their viruses (phages) – from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.

Nanobodies: a tool to open new horizons in diagnosis and treatment of prostate cancer

Background Prostate cancer is one of the most common cancers in men and its incidence has increased dramatically in the last decade. This increase in the detection of this type of cancer is based more on the detection of PSA or PSMA antigens as the most important specific antigens of this cancer, and this early detection has greatly helped in the more optimal treatment of patients. Main body Many methods have been proposed by researchers for early detection of prostate cancer, but most of the methods used today to detect this type of cancer have been using classical antibodies. Although classical antibodies are able to detect tumor cell markers, but instability, large size, costly and laborious production, and random immobility characteristics, causes many problems. Nanobodies or VHHs, which are derived from camel heavy chain antibodies, have special advantages and have eliminated the disadvantages of classical antibodies which makes them attractive to use in biosensors and cancer diagnostic kits. The research that has been done so far shows that the introduced nanobodies are created for the purpose of targeting, detecting and sensing prostate cancer cells with two main purposes. The first is the efficient identification of prostate cancer and the second is the elimination of cancer cells. Conclusion Research shows the use of specific nanobodies against prostate cancer antigens in the design of biosensors and target therapy will be very interesting. In this review article, these nanobodies are introduced and categorized based on their performance.

HLA-B and cysteinylated ligands distinguish the antigen presentation landscape of extracellular vesicles

Extracellular vesicles can modulate diverse processes ranging from proliferation and tissue repair, to chemo-resistance and cellular differentiation. With the advent of tissue and immunological targeting, extracellular vesicles are also increasingly viewed as promising vectors to deliver peptide-based cancer antigens to the human immune system. Despite the clinical relevance and therapeutic potential of such ‘cell-free’ approaches, the natural antigen presentation landscape exported in extracellular vesicles is still largely uncharted, due to the challenging nature of such preparations and analyses. In the context of therapeutic vesicle production, a critical evaluation of the similarity in vesicular antigen presentation is also urgently needed. In this work, we compared the HLA-I peptide ligandomes of extracellular vesicles against that of whole-cells of the same cell line. We found that extracellular vesicles not only over-represent HLA-B complexes and peptide ligands, but also cysteinylated peptides that may modulate immune responses. Collectively, these findings describe the pre-existing provision of vesicular HLA complexes that may be utilized to carry peptide vaccines, as well as the propensity for different peptide and post-translationally modified ligands to be presented, and will outline critical considerations in devising novel EV vaccination strategies.

Cancer Immunotherapy Based on Carbon-Quantum-Dots

Cancer immunotherapy based on carbon-quantum-dots (CQDs) has proven effective. The CQDs composited cancer cell (CM-cancer) exhibit robust customized immunogenicity, which can recruit macrophages and dendritic cells to effectively deliver the cancer antigens into lymph nodes to activate CD8+ T cells, and eventually leads to an anti-cancer immune response all over the body. The CM-cancer is not only able to inhibit primary tumors, but also clearly eliminate metastatic tumors. Our research demonstrates a promising personalized cancer immunotheraputic technology for potential clinical applications.

Nanoparticle T-cell engagers as a modular platform for cancer immunotherapy

T-cell-based immunotherapy, such as CAR-T cells and bispecific T-cell engagers (BiTEs), has shown promising clinical outcomes in many cancers; however, these therapies have significant limitations, such as poor pharmacokinetics and the ability to target only one antigen on the cancer cells. In multiclonal diseases, these therapies confer the development of antigen-less clones, causing tumor escape and relapse. In this study, we developed nanoparticle-based bispecific T-cell engagers (nanoBiTEs), which are liposomes decorated with anti-CD3 monoclonal antibodies (mAbs) targeting T cells, and mAbs targeting the cancer antigen. We also developed a nanoparticle that targets multiple cancer antigens by conjugating multiple mAbs against multiple cancer antigens for T-cell engagement (nanoMuTEs). NanoBiTEs and nanoMuTEs have a long half-life of about 60 h, which enables once-a-week administration instead of continuous infusion, while maintaining efficacy in vitro and in vivo. NanoMuTEs targeting multiple cancer antigens showed greater efficacy in myeloma cells in vitro and in vivo, compared to nanoBiTEs targeting only one cancer antigen. Unlike nanoBiTEs, treatment with nanoMuTEs did not cause downregulation (or loss) of a single antigen, and prevented the development of antigen-less tumor escape. Our nanoparticle-based immuno-engaging technology provides a solution for the major limitations of current immunotherapy technologies.

Cancer Testis Antigens and Immunotherapy: A new Dawn

Immunotherapy for cancer has been recognized as the fourth therapeutic method after surgery, radiotherapy and chemotherapy, which can prevent postoperative metastasis and recurrence and reduce or even eliminate the toxic and side effects of chemoradiotherapy. The development of successful immunotherapy strategies need to use cancer antigens which can be identified by the host’s immune system. This method’s ability in causing antitumor immune response has been fully proved, but it also faces enormous risks and challenges, as finding the highly efficient and specific tumor markers is very difficult. Cancer-testis antigens(CTA) are a special kind of tumor antigens with normal expression restricted to male germ cells in the testis but not in adult somatic tissues. The immune privileged status of CTA gives tumor specificity and makes it an ideal candidate for targeted immunotherapy biomarkers. Here, we briefly review the research history, expression characteristics of CTA, molecular mechanisms of CT gene, and the bright future of immunotherapy in cancer treatment.

Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of many forms of cancer by stimulating body's own immune system. This therapy not only eradicates tumor cells by inducing strong anti-tumor immune response but also prevent their recurrence. The clinical cancer immunotherapy faces some insurmountable challenges including high immune-mediated toxicity, lack of effective and targeted delivery of cancer antigens to immune cells and off-target side effects. However, nanotechnology offers some solutions to overcome those limitations, and thus can potentiate the efficacy of immunotherapy. This review focuses on the advancement of nanoparticle-mediated delivery of immunostimulating agents for efficient cancer immunotherapy. Here we have outlined the use of the immunostimulatory nanoparticles as a smart carrier for effective delivery of cancer antigens and adjuvants, type of interactions between nanoparticles and the antigen/adjuvant as well as the factors controlling the interaction between nanoparticles and the receptors on antigen presenting cells. Besides, the role of nanoparticles in targeting/activating immune cells and modulating the immunosuppressive tumor microenvironment has also been discussed extensively. Finally, we have summarized some theranostic applications of the immunomodulatory nanomaterials in treating cancers based on the earlier published reports.

MUC1 antibody-based therapeutics: the promise of cancer immunotherapy

Antibody-based targeted therapies have been able to target cancers with enhanced specificity and high efficacy. In this regard, identifying cancer markers (antigens) that are only present (tumor-specific antigens) or have an increased expression (tumor-associated antigen) on the surface of cancer cells is a crucial step for targeted cancer treatment. Various cancer antigens have already been used for therapeutic and diagnostic purposes. MUC1 is one of the most important tumor markers with high levels of expression in various solid tumors which makes it as a potential target for antibody-based therapies. This review discusses preclinical and clinical results from various platforms based on monoclonal antibodies, nanobodies as well as bispecific antibodies against MUC1. We also highlight unmet challenges that must be overcome to generate more effective cancer immunotherapy strategies.