The recent advancements in RNA therapeutics have brought to light the need for mRNA molecules that possess better stability and functionality in vivo. Unfortunately, the supply of RNA API has become a bottleneck, hindering progress in the field. In this presentation, we will showcase our optimal in vitro transcription (IVT) manufacturing technique for producing high-performing Cap1 and Cap2 mRNA. Additionally, we will introduce a novel method for preparing circular RNA (circRNAs) to address the short half-life issue of mRNA in vivo, which limits its therapeutic potential. CircRNAs are a unique type of long non-coding RNA that are closed and have covalently linked 5’ and 3’ termini via back-splicing of exons from a single pre-mRNA in nature. A novel method is demonstrated to circularize RNA of interest in vitro and highlight the potential of circRNA to be a promising new class of RNA therapeutics due to their improved stability and longevity.

Learning Objectives:

1. Gain insights into an optimal IVT manufacturing technique for high-performing mRNA production, addressing stability and functionality concerns.

2. Learn about the unique features and advantages of circRNAs as a novel class of therapeutics.

3. Understand the potential of circRNA to overcome the short half-life limitation of linear mRNA, opening new possibilities for RNA-based therapies.

Hematuria (blood in urine) may occur in up to 10% of the general population and results in costly evaluation to ensure it is of no consequence, i.e., no bladder cancer (BCa) is present since hematuria is typically the initial sign of BCa. Furthermore, 75% of patients with newly diagnosed BCa have non-muscle-invasive disease (NMIBC), which has a very high recurrence rate (>70%). Because of this, it is recommended that the patients have adjuvant intravesical bacillus Calmette-Guerin (BCG) instillation to reduce this risk. Despite BCG treatment, up to 50% of patients fail to respond and 20% progress to muscle invasive bladder cancer (MIBC) mandating more radical treatment (i.e., cystectomy - removal of the urinary bladder). Moreover, the delay in radical treatment can negatively impact survival rates, hence, a test that could predict treatment response to intravesical BCG, ensuring the right patient, gets the right treatment at the right time is urgently required. To date, no such test is available. Our group has developed and tested a multiplex immunoassay towards a BCa signature with extremely encouraging results in subjects evaluated for hematuria and in subjects destined to be treated with BCG. This research will open the door for improving on the non-invasive methods for detecting BCa and predicting treatment response as such it will have a marked impact on patient care.

The obesity pandemic is concerning for a multitude of reasons, one of which is the association between increased adiposity, cancer incidence, and higher mortality rates observed in patients who fall within this demographic. The obesity-induced drivers of various subtypes of cancers are under investigation with our group and others attempting to delineate how adipocyte-induced alterations in the immune landscape impact cancer progression and therapeutic responses.

By studying how obesity impacts B-cell acute lymphoblastic leukemia (B-ALL) development, we have found that adipocytes directly decreased chemosensitivity and compromise anti-leukemia immunity. Regarding the latter, we have found that adipocyte-mediated immunosuppression reduces the function of T-cells and myeloid cells, with the former showing compromise proliferative responses, reductions in the production of pro-inflammatory cytokines, and attenuated cytolytic capabilities. Adipocyte-mediated T-cell defects resulted from reductions in genes coding for T-cell signaling machinery and alterations in the ultrastructure of T-cells, which significantly reduced the biomechanical properties of T-cells when they encountered B-ALL cells. Notably, these defects could not be overcome in the presence of the immunotherapy blinatumomab, where human T-cells failed to kill a large percentage of human B-ALL cells in co-culture assays.

Overall, our work demonstrates that adiposity promotes B-ALL development by compromising the function of endogenous T-cells, which reduces the efficacy of T-cell licensing immunotherapies targeting blood cancers.

Learning Objectives:

1. Explain how obesity impacts the survival of pediatric patients with specific subtypes of leukemia.

2. Describe how obesity impacts T-cell function in pediatric populations with and without leukemia.

3.Discuss how adiposity impacts the efficacy of T-cell based immunotherapies targeted at B-cell malignancies.

Cancer is the #1 cause of death by disease in children.   Over the last few decades, the survival rates for children with cancer have improved.  These gains have been made by brilliant dedicated clinicians and researchers, mostly by bringing caregivers and patients together across the country and around the world using traditional clinical trials to optimize interventions like surgery, radiation and chemotherapy.  These treatments are harsh – children go through significant suffering and morbidity during their treatments and often have late effects from these therapies. Molecular tumor profiling is new tool available to us to improve and save the lives of children with cancer. The benefits of molecular profiling and personalized medicine have been demonstrated in adult cancer care, and recently our work has shown that children with cancer also benefit. In children with solid tumors, clinically relevant molecular alterations were identified in most (86%) of patients. Molecular alterations have a substantial impact in making the correct diagnosis, and in matching patients to targeted therapies. Please join us in working towards a future where each child with cancer gets the right test at the right time, gets the right diagnosis and gets the best treatment.  

In the United States, cancer disproportionately impacts Black and African American individuals. Identifying genetic factors underlying cancer disparities has been an important research focus and requires data that are equitable in both quantity and quality across racial groups. It is widely recognized that DNA databases quantitatively underrepresent minorities. However, the differences in data quality between racial groups have not been well studied. We compared the qualities of germline and tumor exomes between ancestrally African and European patients in The Cancer Genome Atlas of 7 cancers with at least 50 self-reported Black patients in the context of sequencing depth, tumor purity, and qualities of germline variants and somatic mutations. Germline and tumor exomes from ancestrally African patients were sequenced at statistically significantly lower depth in 6 out of the 7 cancers. For 3 cancers, most ancestrally European exomes were sequenced in early sample batches at higher depth, whereas ancestrally African exomes were concentrated in later batches and sequenced at much lower depth. For the other 3 cancers, the reasons for lower sequencing coverage of ancestrally African exomes remain unknown. Furthermore, even when the sequencing depths were comparable, African exomes had disproportionally higher percentages of positions with insufficient coverage, likely because of the known European bias in the human reference genome that impacted exome capture kit design. Overall and positional lower sequencing depths of ancestrally African exomes in The Cancer Genome Atlas led to underdetection and lower quality of variants, highlighting the need to consider epidemiological factors for future genomics studies.

Learning Objectives:

1. Summarize the primary explanation for higher total read depth among the TCGA patients with European ancestry compared to those with African ancestry.

2. Define how lower coverage impact germline variants discovery, particularly among patients with African ancestry.

3. Explain how besides lower total read depth, what could have contributed to the enrichment of low-coverage positions among African exomes.

One of the central tenets of biology is that our genetics—our genotype—influences the physical characteristics we manifest—our phenotype. But with more than 25,000 human genes and more than 6,000,000 common genetic variants mapped in our genome, finding associations between our genotype and phenotype is an ongoing challenge. Indeed, genome-wide association studies have found thousands of small effect size genetic variants that are associated with phenotypic traits and disease. The simplest explanation is that genes and genetic variants work together in complex regulatory networks that help define phenotypes and mediate phenotypic transitions. We have found that the networks, and their structure, provide unique insight into how genetic elements interact with each other and the structure of the network has predictive power for identifying critical processes in health and disease and for identifying potential therapeutic targets. Drawing on examples from TCGA, GTEx, and other large data sets, we will explore the ways in which modeling regulatory networks provides insight into functional changes that can drive cancers and point to therapies.

Learning Objectives: 

1. Understand why genetic differences alone are not enough to determine phenotype.

2. Describe the difference between a gene regulatory network and a correlation network.

3. Describe "data shift" and "under-specification" and how prior knowledge of a system can help address the latter.

Neoantigen vaccines are a type of personalized cancer vaccine. While clinical trials have shown promising results, it is important to note that neoantigen vaccines are still in the early stages of development. Further research is needed to develop successful anti-cancer vaccines. For example, one of the challenges is identifying vaccine delivery systems that allow vaccines to be produced quickly and cost-effectively.

In this webinar, we will review neoantigen vaccines and their current status. We will discuss the different vaccine formats, especially peptide and mRNA, and GenScript's solutions for advancing the development of neoantigen vaccines.

Learning Objectives: 

1. Summarize the Neoantigen vaccine introduction and status. 

2. Review the importance of neoantigen peptide for all forms of neoantigen vaccines. 

3. Outline key considerations for mRNA vaccine outsourcing. 

In the world of advanced medical research, the convergence of synthetic biology and cellular immunotherapy has inaugurated a new era in field of cancer treatment. Simultaneously, life science research continues to reshape our approach to tackling a broad spectrum of human diseases through innovations in gene and cell engineering, expediting crucial advancements. In this rapidly evolving landscape, there's a clear demand for diverse tools to skillfully reprogram and engineer cells for various applications. GenScript Life Science keenly acknowledges this requirement and provides an extensive range of services and products tailored to facilitate the progress of biological-Life Science research and the development of therapeutic solutions.

Learning Objectives: 

1. Recognize important tools utilized at each stage of Cell and Gene Therapy (CGT) discovery.

2. Learn about innovative methodologies for gene and cell engineering.

3. Explore GenScript's Solutions for advancing the development of immuno-therapeutics.

Transmembrane proteins play a critical role in signal transduction, cell adhesion, nutrient uptake, and immune response modulation. However, dysregulation of transmembrane proteins can contribute to tumor initiation, metastasis, and evasion of immune surveillance. Unraveling their intricate roles provides valuable insights for the development of targeted therapies and personalized treatment strategies. Researchers are now harnessing the knowledge of transmembrane protein interactions to design bispecific antibodies that precisely redirect the immune system to attack tumors specifically. Amid the ever-evolving landscape of life science research, Sino Biological stands at the forefront of innovation with its cutting-edge transmembrane protein production platforms. We are proud to introduce a game-changing solution that empowers researchers in oncology: advanced and customizable transmembrane protein production services. Our state-of-the-art platforms, including Virus-like Particle (VLP), Nanodiscs, and Detergent micelles, accelerate the pace of discovery in cancer research. This webinar will shed light on the significance of transmembrane proteins in oncology research and their potential as therapeutic targets.

Learning Objectives:

1. Outline the role of transmembrane proteins in drug discovery.

2. Review the transmembrane protein production platforms: virus-like particle (VLP), nanodisc, and detergent micelles platforms.

3. Outline the current landscape of therapeutic antibodies targeting membrane proteins.

We started our experience with prostate cancer in 2002 with primitive robotic platforms. Our main goal was to provide an alternative to open and laparoscopic surgery. In this scenario, the evolution of new platforms optimized and improved surgical outcomes, and robotic surgery became the standard of care in centers with access to this technology.

Even with technological improvements and several robotic platforms in the market, the treatment of prostate cancer is still challenging because it depends on numerous factors such as patient age, sexual function, tumor histology and staging, surgical technique, and patient compliance with postoperative rehabilitation protocols.

Furthermore, in recent years, we have witnessed some changes in the oncologic nature of prostate cancer and an increase in more aggressive tumors, which negatively affected postoperative functional and oncological outcomes. In this context, we modified our surgical technique several times to maintain our positive surgical margin rates and provide optimal oncological treatment for our patients.

Our team has been publishing several scientific articles describing our surgical technique and outcomes of postoperative recovery of potency, continence, and cancer control. However, prostate cancer still challenges patients and surgeons, and we are still working hard to provide and improve outcomes. There is a trend toward operating on higher-risk patients, large-volume tumors, oligometastatic tumors, and salvage surgery due to increasing rates of these cases in recent years. Technical modifications have also allowed us to keep margins and short-term oncologic outcomes stable. However, the quality of the candidates for full nerve-sparing surgery has reduced.

In the near future, we foresee a continued increase in high-risk and metastatic prostate cancer. We believe educating our PCP physicians and Urologists to perform PSA screening and DRE is important to reduce the rates of aggressive cancers, and advanced imaging such as PSMA PET will play a role in stratifying patients who will and will not benefit from local surgery or radiation therapy.

Learning Objectives:

1. Evaluate and analyze the surgical techniques and methodology behind complex robotic prostate cancer surgeries.

2. Describe the key complications and outline the intra-operative and post-operative management related to robotic prostatectomy using video-based learning and didactic presentation.

3. Demonstrate current and upcoming protocols for regaining potency and continence following robotic prostatectomy.

In the ever-evolving landscape of cancer therapy, immune checkpoint inhibitors have emerged as promising avenues for therapeutic antibody development. Our presentation will share GenScript's comprehensive suite of products and services tailored to empower scientists in the field of cancer therapeutic antibody development with emphasis on Immune Checkpoints. Join us as we explore how GenScript's innovative solutions, ranging from antibody generation to bioassay development, protein expression, and beyond, can accelerate your efforts in harnessing the power of immune checkpoint inhibitors to combat cancer.

Learning Objectives:

1. Explore GenScript's custom antibody generation and optimization services tailored for immune checkpoint proteins.

2. Learn about high-quality protein expression services for immune checkpoint studies.

3. Gain insights into cell line development and its role in stable expression of immune checkpoint proteins.

The tumor-associated microbiota is an inherent component of the tumor microenvironment across various human cancer types1. Although members of tumor-associated microbiomes can be identified through 16S rRNA analysis, physical access to bacterial isolates facilitates functional and mechanistic studies to determine the role of these bacterial species in cancer initiation, progression, and patient response to treatment. Here, through complimentary application of large-scale culturing techniques and bacterial single-cell whole genome sequencing approaches, we isolated three novel bacterial species across four tumor tissue samples from patients with colorectal cancer, including a novel Fusobacterium species2. Utilizing PacBio Single Molecule Real Time (SMRT) sequencing we obtained complete genomes for all three novel bacterial species, which facilitated comparative genomics to identify the nearest species neighbors and bioinformatic analyses to distinguish genetic factors that are uniquely present in these tumor isolates. These analyses will inform future mechanistic studies to understand the capabilities and roles of these novel bacterial species.

Learning Objectives:

1. Describe the advantages and disadvantages of various techniques and technologies to identify and culture bacterial species from a tissue-associated microbial community.

2. Explain why physical access to bacterial isolates can be a powerful advantage to microbiologists.

3. Discuss at least two approaches by which the novelty of a bacterial species can be confirmed.

Neoantigens are peptides derived from patient-specific and tumor-specific mutations, which can be recognized by the immune system and mediate tumor recognition that leads to immune destruction of the cancer. Neoantigens are emerging as one of the next generation immuno-oncology targets with tremendous potentials. Neoantigen can be identified by bioinformatics analyses of tumor DNA and RNA sequencing data include three steps. In this talk, I will introduce the definition, identification, prioritization of the neoantigens using tumor sequencing data. I’ll describe our REAL-neo analytic framework, including several novel modules implemented in the newest version of the pipeline.

Learning Objectives:

1. Introduce the background of neoantigens, and how neoantigens work against cancer.

2. Identify and validate neoantigens: the REAL-neo framework.

3. Explain the application of neoantigen vaccines: example of an individual patient investigational new drug (IND) trial.

The elegant and well-orchestrated molecular players responsible for normal neurodevelopment harbor the capacity for detrimental repercussions if mis-expressed at the wrong time, or in the wrong place. With a background in developmental neuroscience and subsequent training in cancer biology, I have long been interested the brain's capacity for change. Combining these distinct yet overlapping fields, my lab utilizes genetic mouse models to explore both normal and abnormal plasticity and the link between these processes in tumors of the central nervous system (CNS). By exploring the role of neurotrophins (a family of proteins important for brain function) and their receptors in development, I hope to gain a better understanding of what makes certain cancers grow so that we can figure out how we might develop novel therapeutics. I am particularly interested in how various neurotrophic and genetic factors can influence the development, survival, and behavior of various cell types within and outside the CNS in normal development and more importantly how these processes can be hijacked in cancer. Important for establishing the developing nervous system, this family of proteins (called the neurotrophin receptors) is very tightly regulated at the DNA, RNA, and protein level. Recent work from our group has shown that a particular change at the RNA level results in a unique variation of a neurotrophin receptor called tropomyosin receptor kinase B, or TrkB. This particular TrkB variant is expressed at very high levels in adult and pediatric cancers, including brain tumors. Forced expression of this receptor causes multiple cancer types in our mouse model, suggesting that it is both a marker and driver of oncogenesis – and a potentially druggable target, highlighting the importance of investigating splice variants in basic and translational research.

Learning Objectives:

1. Summarize the neurotrophin family of receptors and their roles in neurodevelopment and oncology.

2. Explain the role alternative splicing in gliomas, using TrkB.T1 as an example.

3. Review the importance of studying alternative splicing in normal development and pediatric & adult cancers.

Over the past 10 years, we have come to a greater understanding of the pathogenesis of men who succumb to prostate cancer. One critical aspect is the role of molecular drivers in patients with higher grade disease and the implications in management for both localized and advanced prostate cancer. In order to best manage these patients, the provider needs a basic comprehension of the role and rationale of genetic testing, how to best categorize the various genes involved in prostate cancer development and incorporate this into their practice. This presentation will give the provider a foundation to simplify the complexity and understanding of genomic testing and the role of the urologist.

Learning Objectives: 

1. Differentiate Germline vs Somatic Testing.

2. Categorize the genes associated with different DNA repair pathways.

3. Review the different types of genetic mutations and classifications.

Conventional imaging studies such as ultrasound, computed tomography, and magnetic resonance imaging are increasingly detecting small renal masses, which are interpreted by radiologists as highly suspicious for renal cell cancer. However, up to 30% of these small solid tumors (<4 cm) are in fact found to be benign on surgical excision. This highlights a significant limitation in conventional radiologic imaging studies in sub-stratifying which patient require active treatment (i.e. surgery versus thermal ablation) versus surveillance. It also highlights a tremendous opportunity for investigations into how advanced imaging technologies could play a role in radically changing the current paradigm in the management of small renal tumors. New imaging technologies such as advanced cross-sectional imaging, molecular imaging and optical imaging show promise in improving pre-treatment risk categorization with the hopes of reducing unnecessary treatment. Together radiologists, urologists, and computer imaging experts amongst others have the opportunity to discover, develop and test new diagnostic imaging modalities to improve patient care.

Learning objectives:

1. Recognize the relatively high incidence of benign tumors found following renal tumor surgery for small renal masses.

2. Identify the limitations of conventional cross-sectional imaging in characterizing small renal masses.

3. Describe how new advanced imaging modalities may in the future help predict tumor phenotype and thus reduce the number of unnecessary treatments of benign or low risk renal tumors.

Immuno-oncology (IO) is a type of cancer treatment that uses the body's immune system to fight cancer. It works by stimulating the immune system to recognize and attack cancer cells, while leaving healthy cells unharmed. IO therapies can include immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, among others. IO is a rapidly developing field in cancer research and has shown promising results in treating various types of cancer. A rapid increase in recent clinical approvals has been seen, for both cell-based and antibody approaches. However, many obstacles remain in the development and understanding of these therapeutics. Through the introduction of live-cell analysis, researchers can increase their biological insights in supporting the development of future therapeutics.

Learning Objectives:

1. Explain how live-cell analysis can be incorporated into development workflows.

2. Explain how live-cell analysis can provide efficient, biological insight for biotherapeutics.

3. Summarize how the case study data supports the use of Incucyte® Live-Cell Analysis Systems.

Discover how experience in utilizing a digital lab platform can elevate research workflows. Margriet will share insights, practical strategies, and success stories that demonstrate the benefits a digital lab platform can bring to your research endeavors. This webinar is your opportunity to delve into the world of cutting-edge technology and amplify your efforts in cancer research.

What's in it for you?
Streamlined Research
Workflows
Innovative Techniques
Interactive Q&A

Radiation therapy is an important cornerstone of oncologic therapy but is feared to the point of intimidation by too many patients. Yet by the end of treatment, most patients find the experience of radiation therapy to be more pleasant than they had feared. With just a few simple words of patient education, medical oncologists and surgical oncologists can help alleviate some of that fear even before the patient sees the radiation oncologist. This talk provides a different approach to tangibly understanding radiation therapy for what it is (rather than simply saying that it usually won’t make a patient radioactive). The talk addresses the most common form of radiation therapy, LINAC-based external beam radiation therapy.

Learning Objectives:

1. Summarize how radiation therapy is treatment with waves of energy.

2. Explain how radiation therapy is a form of “light” therapy.

3. Explain how linear accelerators work on the same principles as a room lamp.

4. Review how patients are not radioactive or exposed to radioactivity.

Informed consent (IC) is a fundamental aspect of ethical clinical research, safeguarding the rights and well-being of participants. It empowers participants with comprehensive information about the research, enabling them to make voluntary and informed decisions about their participation in the research after understanding all risks and benefits associated with the research. A robust IC process holds particular relevance in the context of cancer research, where inadequate communication can strain patient-researcher relationship and trust, jeopardizing entire research studies. Furthermore, the level of subject understanding directly correlates with engagement throughout the research journey. Research indicates that well-informed subjects are more likely to stay engaged and continue participating in the study until its completion, leading to more meaningful research outcomes. High retention rates are crucial for the statistical power and integrity of the research. Thus, in cancer research, IC transcends mere regulatory compliance; it acts as a critical compass guiding the ethical conduct of cancer research. However, challenges persist in obtaining and ensuring meaningful IC, including information or comprehension gaps, limited understanding, and potential pressures on participants. It is crucial for researchers to address these challenges to uphold the principles of autonomy and protect participants' interests. To facilitate the IC process, a Laboratory Information Management System (LIMS) emerges as a valuable tool. It offers a secure platform to manage participant consent. By anonymizing Protected Health Information (PHI) and providing secure data management, a LIMS ensures the confidentiality of participants. It also streamlines document management, granting researchers access to the latest approved consent forms, and aids in associating participants with specific studies, enhancing the traceability and integrity of the IC process in cancer research.

Learning Objectives:

1. Summarize what Informed Consent (IC) is, and the challenges and benefits of obtaining IC in cancer research.

2. Describe what the basic and additional elements for IC writing are under the FDA and Common Rule.

3. Explain how a LIMS can help manage IC.

Natural killer (NK) cells, immune cells with an innate ability to recognize and eliminate cancer cells, have emerged as attractive effectors in immunotherapy, owing in large part to their ability to target cancers based on MHC ligand mismatch, thus representing a source of potentially allogeneic immune cells, and a safer alternative to T cells. As such, various approaches aimed at exploiting NK cells for immunotherapy have been in development. These approaches have leveraged genetic engineering as a tool to regulate NK cell activation in terms of controlling their anti-tumor function, metabolism and persistence, and have shown promise as anti-cancer therapies. However, targeting complex cancers such as aggressive solid tumors remains a challenge due to profound immunosuppression in the microenvironment of such cancers, which dampens not only NK cell, but also other immune effector responses. In this talk, we discuss opportunities for NK cells in immunotherapy, including novel genetic engineering approaches and therapeutic modulation strategies aimed at enhancing NK cell immune responses, with the ultimate goal to effectively and durably targeting currently uncurable cancers.

Learning Objectives:

1. Understand and summarize how natural killer cells recognize and eliminate cancers.

2. Describe methods to enhance and regulate natural killer cell activity in tumors in the context of immunotherapy.

3. Explain challenges in targeting the tumor microenvironment in cancer.

Effective cellular therapies for solid tumors remain elusive. Advances in gene editing and synthetic biology offer great potential for improving the safety and functionality of engineered cellular medicines, but traditional discovery technologies in human immune cells are time-consuming and low-throughput. To overcome these issues, we developed non-viral genome targeting, a method for large-scale genetic engineering of diverse primary human immune cells overcoming the challenges of traditional viral vectors. We further developed pooled knockin screening, enabling rapid discovery of novel sequences to re-wire human immune cell genomes. Further extensions of pooled knockin sequencing have now enabled a high throughput, modular and highly scalable platform to rapidly associate large pools of T cell genetic modifications with high dimensional single cell phenotypes across diverse disease contexts. The resulting genotype x phenotype maps have nominated unique novel cell therapy targets with improved in vitro and in vivo performance for further clinical development.

Learning Objectives:

1. Summarize how synthetic genes can be integrated specifically at endogenous genes to engineer T cell specificity.

2. Describe some benefits of pooled screening systems.

3. Explain how pooled genetic perturbations can be combined with high dimensional single cell phenotypes.