MUC1 antibody-based therapeutics: the promise of cancer immunotherapy

Immunotherapy ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 1269-1286
Author(s):  
Mona Pourjafar ◽  
Pouria Samadi ◽  
Massoud Saidijam
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Immunotherapy ◽  
Clinical Results ◽  
Bispecific Antibodies ◽  
High Efficacy ◽  
Cancer Markers ◽  
Crucial Step ◽  
Cancer Antigens ◽  
Tumor Associated Antigen ◽  
Specific Antigens

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.

Modulation of Immune and Anti-Tumor Effects of Cancer Immunotherapy with Anti-Pd-1 Monoclonal Antibodies by the Pineal Hormone Melatonin: Preliminary Clinical Results

2020 ◽  
Author(s):  
Simonetta Tassoni
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Immunotherapy ◽  
Metastatic Cancer ◽  
Concomitant Administration ◽  
Clinical Results ◽  
Control Group ◽  
High Dose ◽  
Main Question ◽  
Anticancer Properties ◽  
Inflammatory Status

The recent cancer immunotherapy with inhibitors of the expression of PD-1 and its ligands represents one of the most promising strategies in cancer cure. Then, the main question is how to enhance its therapeutic efficacy, which could potentially achieved by its association with chemotherapy, Il-2 immunotherapy, and anti-angiogenic strategies. By taking into consideration that the immune system is physiologically under a neuroendocrine regulation, another possible strategy to enhance the efficacy of cancer immunotherapy could consist of a neuro immune approach, namely by the pineal hormone melatonin (MLT), which at present constitutes the most investigated endogenous neuroendocrine molecule provided by immune stimulatory anticancer properties. On these bases, a study was planned to evaluate the effects of a concomitant administration of high-dose MLT in metastatic cancer patients treated by the anti-PD-1 monoclonal antibody Nivolumab (NIVO). The study included 14 patients, and the results were compared to those observed in a control group of 50 patients. No small cell lung cancer and melanoma were the most frequent tumor histo types. MLT was given orally at 100 mg/day during the dark period of the day, and NIVO was injected i.e. at 3 mg/kg b.w. at 15-day intervals. The percentage of both objective tumor regressions and disease control (DC) were higher in patients concomitantly treated by MLT, even though the only difference in DC was statistically significant. This evidence was associated with a significantly higher increase in lymphocyte-to-monocyte ratio (LMR) in MLT group, by suggesting that MLT may be successfully associated with anti-PD-1 monoclonal antibodies to pilot the immune response in an antitumor way by stimulating lymphocyte proliferation and inhibiting macrophage-induced inflammatory status, which suppresses the antitumor immunity.

scholarly journals The Next-Generation of Combination Cancer Immunotherapy: Epigenetic Immunomodulators Transmogrify Immune Training to Enhance Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3596
Author(s):  
Reza Bayat Mokhtari ◽  
Manpreet Sambi ◽  
Bessi Qorri ◽  
Narges Baluch ◽  
Neda Ashayeri ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Tumor Antigens ◽  
Response Rates ◽  
Viral Proteins ◽  
Tumor Rejection ◽  
Therapeutic Approaches ◽  
Patient Response ◽  
Specific Antigens

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy.

scholarly journals Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1999
Author(s):  
Annacarmen Petrizzo ◽  
Concetta Ragone ◽  
Beatrice Cavalluzzo ◽  
Angela Mauriello ◽  
Carmen Manolio ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Genetic Material ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Danger Signal ◽  
Human Endogenous Retroviruses ◽  
Double Stranded Rna ◽  
Specific Antigens ◽  
Viral Mimicry

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a “danger signal” by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs). Alternatively, HERV reactivation is associated with the expression of long noncoding RNAs (lncRNAs). In this review, we will highlight recent findings on HERV reactivation in cancer and its implications for cancer immunotherapy.

Sperm antigens and immunocontraception

1995 ◽  
Vol 7 (4) ◽  
pp. 825 ◽  
Author(s):  
LE Kerr
Keyword(s):  
Monoclonal Antibodies ◽  
World Population ◽  
Contraceptive Vaccine ◽  
The World ◽  
Specific Antigens ◽  
Population Crisis ◽  
Sperm Antigens

The development of novel forms of contraception is one way in which the world population crisis is being tackled. The concept of a contraceptive vaccine based on gamete-specific antigens is a particularly attractive approach. Much research has been carried out to identify sperm antigens which could be used as the immunogen. The most encouraging leads have come from groups using monoclonal antibodies to identify and characterize sperm antigens important for fertility (e.g. SP-10, PH-20 and PH-30). Identification of these molecules will also enable the development of specific tests for the diagnosis of immune infertility.

Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Jun Lin ◽  
Binbin Ding ◽  
Pan Zheng ◽  
Dong Li ◽  
Meifang Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
High Specificity ◽  
The Body ◽  
Immunogenic Cell Death ◽  
Specific Antigens

Cancer vaccine is to make tumor-specific antigens into vaccines, which then are injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic...

scholarly journals Cancer Immunotherapy with Immunomodulatory Anti-CD137 and Anti–PD-1 Monoclonal Antibodies Requires BATF3-Dependent Dendritic Cells

2015 ◽  
Vol 6 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Alfonso R. Sánchez-Paulete ◽  
Francisco J. Cueto ◽  
María Martínez-López ◽  
Sara Labiano ◽  
Aizea Morales-Kastresana ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Monoclonal Antibodies ◽  
Cancer Immunotherapy

Passive-specific immunotherapy with monoclonal antibodies for prostate cancer: A systematic review

2018 ◽  
Vol 25 (4) ◽  
pp. 903-917 ◽  
Author(s):  
Neda Khalili ◽  
Mahsa Keshavarz-Fathi ◽  
Sepideh Shahkarami ◽  
Armin Hirbod-Mobarakeh ◽  
Nima Rezaei
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Monoclonal Antibodies ◽  
Advanced Prostate Cancer ◽  
Search Strategy ◽  
Specific Immunotherapy ◽  
Therapeutic Option ◽  
Grey Literature ◽  
Statistical Heterogeneity ◽  
Specific Antigens

Introduction Treatment of metastatic castration-resistant prostate cancer with conventional therapies is still not successful. Therefore, application of novel biological approaches such as immunotherapy, which appears to be more effective and less toxic, is necessary. Monoclonal antibodies against cancer specific antigens are a kind of immunotherapy that have been approved for specific types of cancer and are being investigated for prostate cancer as well. The aim of this review was to assess the effectiveness and safety of monoclonal antibodies for treatment of advanced prostate cancer. Method According to the search strategy stated in our systematic review protocol, Scopus, Medline, TRIP, CENTRAL, ProQuest, DART and OpenGrey databases were searched. Data collection and quality assessment were done independently by two authors and any disagreements between the collected data were resolved by a third author. A meta-analysis was not feasible as there was a considerable statistical heterogeneity among the trials. Hence, this review was limited to a narrative analysis of the included studies. Results We found 9756 references by applying search strategy in 4 databases of journal articles and 3 databases of grey literature. We then discarded 3957 duplicate citations using Endnote software and 5143 articles due to obvious irrelevancy of their topics in primary screening. In secondary screening of 656 fulltexts, we excluded 538 articles, and finally included 12 trials in this systematic review, updated on 23 June 2017. The overall quality of the studies was fair. In general, results of this systematic review show promising advances in the treatment of prostate cancer patients with monoclonal antibodies against prostate-specific antigens with regard to PSA/disease response. Some of the studies reported pain relief after treatment as well. Conclusion Currently, the role of immunotherapy in the treatment of advanced prostate cancer still remains debated. Although passive specific immunotherapy could be offered as a novel therapeutic option in the coming years, patients should be informed about the risks and benefits of this therapy. One of the obstacles in this review was the lack of adequate assessment of survival-related endpoints reported in the included studies. Our study provides support for further research in this field.

scholarly journals Treatment of rheumatic immune-related adverse events due to cancer immunotherapy with immune checkpoint inhibitors—is it time for a paradigm shift?

2020 ◽  
Author(s):  
Katerina Chatzidionysiou ◽  
Matina Liapi ◽  
Georgios Tsakonas ◽  
Iva Gunnarsson ◽  
Anca Catrina
Keyword(s):  
Adverse Events ◽  
Cancer Immunotherapy ◽  
Potential Risk ◽  
Immune Checkpoint ◽  
Paradigm Shift ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Current Evidence ◽  
Inadequate Response ◽  
High Efficacy

Abstract Immunotherapy has revolutionized cancer treatment during the last years. Several monoclonal antibodies that are specific for regulatory checkpoint molecules, that is, immune checkpoint inhibitors (ICIs), have been approved and are currently in use for various types of cancer in different lines of treatment. Cancer immunotherapy aims for enhancing the immune response against cancer cells. Despite their high efficacy, ICIs are associated to a new spectrum of adverse events of autoimmune origin, often referred to as immune-related adverse events (irAEs), which limit the utility of these drugs. These irAEs are quite common and can affect almost every organ. The grade of toxicity varies from very mild to life-threatening. The pathophysiological mechanisms behind these events are not fully understood. In this review, we will summarize current evidence specifically regarding the rheumatic irAEs and we will focus on current and future treatment strategies. Treatment guidelines largely support the use of glucocorticoids as first-line therapy, when symptomatic therapy is not efficient, and for more persistent and/or moderate/severe degree of inflammation. Targeted therapies are higher up in the treatment pyramid, after inadequate response to glucocorticoids and conventional, broad immunosuppressive agents, and for severe forms of irAEs. However, preclinical data provide evidence that raise concerns regarding the potential risk of impaired antitumoral effect. This potential risk of glucocorticoids, together with the high efficacy and potential synergistic effect of newer, targeted immunomodulation, such as tumor necrosis factor and interleukin-6 blockade, could support a paradigm shift, where more targeted treatments are considered earlier in the treatment sequence.

scholarly journals Antigen Selection for Enhanced Affinity T-Cell Receptor–Based Cancer Therapies

2016 ◽  
Vol 21 (8) ◽  
pp. 769-785 ◽  
Author(s):  
Emma S. Hickman ◽  
Martine E. Lomax ◽  
Bent K. Jakobsen
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
De Novo ◽  
Cell Receptor ◽  
T Cell Response ◽  
Adoptive Cell Transfer ◽  
Cytotoxic T Cell ◽  
Discovery Process ◽  
Cancer Antigens ◽  
The Impact

Evidence of adaptive immune responses in the prevention of cancer has been accumulating for decades. Spontaneous T-cell responses occur in multiple indications, bringing the study of de novo expressed cancer antigens to the fore and highlighting their potential as targets for cancer immunotherapy. Circumventing the immune-suppressive mechanisms that maintain tumor tolerance and driving an antitumor cytotoxic T-cell response in cancer patients may eradicate the tumor or block disease progression. Multiple strategies are being pursued to harness the cytotoxic potential of T cells clinically. Highly promising results are now emerging. The focus of this review is the target discovery process for cancer immune therapeutics based on affinity-matured T-cell receptors (TCRs). Target cancer antigens in the context of adoptive cell transfer technologies and soluble biologic agents are discussed. To appreciate the impact of TCR-based technology and understand the TCR discovery process, it is necessary to understand key differences between TCR-based therapy and other immunotherapy approaches. The review first summarizes key advances in the cancer immunotherapy field and then discusses the opportunities that TCR technology provides. The nature and breadth of molecular targets that are tractable to this approach are discussed, together with the challenges associated with finding them.

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