Catalina Garcia CRP Protein

Immunotherapy has become a revolution in the area of cancer treatment. Compared to the traditional methods, such as invasive surgeries, radiation and chemotherapy, immunotherapy is more specific and less toxic to patients. Chimeric antigen receptor (CAR)-engineered T cell therapy is the most promising approach, which has shown remarkable ability to eliminate various kinds of tumors, especially for B cell malignancies, with up to 95% response rates and durable complete remission.
For more information: car t cell production

Creative Biolabs offers a battery of rodent models including chemically- and surgically- induced OA models for studies of disease mechanisms as well as the testing of therapeutic candidates. We have talented experts and scientists who are willing to help to set up a detailed research plan based on your specific needs. Herein, you can find the most comprehensive services with the most reasonable prices.
For more information: mia model

Although many types of disease models such as immortalized cell systems have been developed, it is challenging to design disease models that involve multiple genes and mimic in vivo human disease state during disease research. iPSCs (induced pluripotent stem cells) that can differentiate into any cell type have emerged as an effective platform for the construction of disease models.
For more information: iPSC for Disease Model Construction

Monoclonal antibody-based immunotherapies against cancer and other infectious diseases are highly advantageous comparing to conventional therapeutic approaches due to their high specificity and affinity towards well-defined targets. Antibody-drug conjugates (ADCs) inherit such superiorities and more remarkably, expand the therapeutic window of the conjugated drugs (payloads), which are usually highly toxic and diverse in their biochemical nature. For more information: abc laboratories

Cancer immunotherapy has shown great promise in cancer treatment over the last decade. Several cancer immunotherapies, such as immune checkpoint blockade therapies, cancer vaccines, and CAR-T therapies, have been extensively researched and have yielded promising results.

Cancer vaccines, which elicit tumor-specific immune stimulation, are one of the most important immunotherapeutic strategies and have great potential in cancer treatment. Patients have responded favorably to cancer vaccines based on neoantigens and messenger RNA (mRNA).

Despite enormous efforts in the development of cancer vaccines, which are still in the cancer prevention phase, eliciting a large number of immune responses in cancer patients remains a significant challenge, owing to the cancer vaccines' low immunogenicity, the immunosuppressive tumor microenvironment, and the ground correlation between antigens in cancer vaccines and specific patient tumors.

Autologous tumors have been used to produce cancer vaccines in vitro or in vivo, so-called personalized cancer vaccines, to improve the therapeutic efficacy of cancer vaccines. Autologous tumor cell-based cancer vaccines benefit from tumor-specific tumor-associated antigens (TAA) and induce a stronger immune response than conventional cancer vaccines.

However, in vitro preparation of autologous tumor cell cancer vaccines suffers from complex processes, low yields, and suboptimal efficacy, which limit the clinical application of autologous tumor vaccines. In contrast, large-scale in situ generation of autologous tumor cell cancer vaccines in vivo avoids the complex in vitro vaccine preparation process and is ideal for the production of cancer vaccines.

On November 1, 2022, Fu-Gen Wu's team from Southeast University's School of Bioscience and Medical Engineering published a research paper in Nature Communications titled: In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses. HDDT nanoparticles were created using dendritic polymers loaded with adriamycin (DOX), tyrosine kinase inhibitor (TKI), and hyaluronic acid (HA) encapsulated nanoparticles. HDDT nanoparticles have the ability to convert 100% of cancer cells into micron-sized vesicles (HMVs).

Experiments in tumor mouse models revealed that HDDT nanoparticles could inhibit tumor growth, induce strong immunogenic cell death, and convert primary tumors into antigenic reservoirs by producing HMVs in situ as personalized cancer vaccines for cancer immunotherapy. Furthermore, after HDDT nanoparticle treatment, tumor model mice showed strong immune memory effects, which could prevent tumor recurrence in the long run.

In this study, the research team fabricated a series of nanobombs (NBs), including dendritic polymers (Dendritic Polymers) loaded with adriamycin (DOX, an anti-cancer drug) and tyrosine kinase inhibitors (TKI, an anti-cancer drug) and hyaluronic acid (HA, used for tumor targeting) encapsulation, called HDDT NBs.

The team found that after treatment of cancer cells with HDDT NBs, almost all cells (10-30 microns in diameter) were transformed into uniform micron-sized vesicles (1.6-3.2 microns), and cell-to-vesicle conversion efficiency was as high as 100%, meaning that all cancer cells could be efficiently converted into HDDT-induced micron-sized vesicles (HMVs).

Further studies revealed that HDDT NBs, after systemic administration, could accumulate in tumor areas, inhibit tumor growth under different tumor models, induce immunogenic cell death on a large scale, and produce HMVs in situ, transforming tumor tissues into antigenic reservoirs. Immune checkpoint blockade therapy, alone or in combination, could induce intra-tumor and systemic immune responses, establish a strong immune memory effect, cure mouse tumors, and effectively protect against recurrence.

Overall, the HDDT-induced micron-sized vesicles (HMVs) developed in this study provide a simple and promising nanotechnology-based strategy for the in situ production of autologous tumor cell vaccines and may provide clues for the development of personalized cancer vaccines.
 

In cancer immunotherapy, the spotlight has fallen on STING as a pivotal target of recent interest. Biopharmaceutical companies worldwide are vigorously developing innovative therapies targeting STING with the goal of activating immune pathways to combat cancer cells.

While these STING agonists have demonstrated promise in preclinical studies, a perplexing phenomenon has emerged in certain clinical trials. Contrary to expectations, drugs designed to activate the STING pathway have not consistently yielded the desired benefits for advanced cancer patients. For instance, a Phase 1 clinical trial assessing STING agonists reported only one out of 47 patients with advanced or metastatic cancer displaying a definitive partial response. In another Phase 1 clinical trial involving a STING agonist co-administered with a PD-1 inhibitor, the overall remission rate for advanced cancer patients hovered around 10%.

So, what accounts for the unexpected outcomes of STING agonists in the fight against cancer? In their quest for answers, researchers at the Memorial Sloan Kettering Cancer Center, in collaboration with Weill Cornell Medicine, have uncovered a counterintuitive possibility—drugs inhibiting STING activation may prove more beneficial to patients with advanced cancer than STING activators.

This revelation hinges on the nature of the STING signaling pathway itself. Within the human body, the presence of double-stranded DNA molecules in the cytoplasmic matrix serves as an early warning signal, indicating the intrusion of pathogens, the existence of cancer cells, or cell rupture. Once intracellular sensors detect cytoplasmic DNA, they activate the STING protein, which, in turn, triggers the expression of inflammation-associated genes, igniting an innate immune response that shields the body from foreign invaders and abnormal cells—a pivotal process in anti-tumor immunity.

However, the new study suggests that cancer cells disrupt the STING signaling pathway, creating an immunosuppressive tumor microenvironment. Particularly in advanced cancer stages, where cancer cells exhibit high chromosomal instability, the STING pathway remains persistently active, leading to "desensitization." This, in turn, rewires the downstream signaling pathway, inducing endoplasmic reticulum stress—a favorable environment for cancer cell metastasis.

Dr. Samuel Bakhoum, co-corresponding author of the study, analogizes this phenomenon, "think of STING signaling as a car alarm. If it rarely sounds, the loud noise will grab your attention. But if it keeps going off, you become accustomed to it and tune it out."

To understand the interactions between cancer cells and immune cells in the tumor microenvironment, another co-corresponding author, Dr. Ashley Laughney, led the team in developing a specialized computational tool named "Contact Tracing". This tool predicts cell-cell interactions and assesses how ligand-receptor interactions influence signal-receiving cells based on single-cell sequencing data.

Dr. Laughney highlights a significant discovery, "one of our most crucial findings is that altering the degree of chromosomal instability or activating STING significantly changes the response within the tumor and its surroundings."

The researchers confirmed the link between chromosomal instability-driven cancer cell metastasis and STING signaling in mouse models implanted with various tumor cells, as well as in human healthy cells and tumor samples. These findings also open the door to innovative therapeutic concepts—for advanced cancer patients with chromosomal instability, activating STING may prove ineffective due to cellular desensitization". In such cases, inhibiting STING could be a promising alternative.

In experimental settings, the researchers administered STING inhibitors to mouse models of melanoma, breast cancer, and colorectal cancer, effectively reducing metastasis driven by chromosomal instability.

Additionally, these insights suggest that by identifying tumors still capable of robust responses to STING activation, clinicians can select patients who would genuinely benefit from STING agonist therapy.

Therapeutic antibodies, engineered through biotechnology, represent a specialized class of antibodies used in disease treatment. These antibodies are designed to target specific disease markers, such as malignant tumors, autoimmune disorders, and infectious diseases. Compared to traditional antibody therapies, therapeutic antibodies offer higher specificity and fewer side effects.

In the realm of immunotherapy, antibody-dependent cell-mediated cytotoxicity (ADCC) stands out as a highly effective anti-tumor mechanism. ADCC enhancement refers to the bolstering of immune cells' ability to attack malignant cells, thereby enhancing the efficacy of immunotherapy. ADCC enhancement technology finds significant applications in the field of therapeutic antibodies, encompassing techniques like fucosylation engineering, Fc protein-engineering, cross-isotype engineering, and glyco- and Fc protein dual engineering.

Furthermore, antibody-dependent cell phagocytosis (ADCP) plays a pivotal role in the action of therapeutic antibodies. The ADCP assay serves as an experimental method for studying antibody-dependent cell phagocytosis. This research investigates whether antibodies assist immune cells, such as macrophages, in recognizing, engulfing, and digesting labeled target cells or pathogens. Through the ADCP assay, researchers can assess whether therapeutic antibodies activate immune cells to attack and eliminate tumor cells, instilling renewed optimism in cancer treatment.

CDC enhancement, a classical approach to fortifying the immune system, amplifies the cytotoxicity of antibodies. Immunotherapy often hinges on antibody action, and CDC enhancement accentuates the activation of the complement system by antibodies, inducing cell toxicity and ultimately eradicating target cells.

In CDC enhancement, antibodies (typically therapeutic monoclonal antibodies) bind to antigens on the surface of target cells, triggering the activation of the C1q molecule in the complement system. C1q further instigates the complement cascade reaction in the immune system, culminating in the formation of the membrane attack complex (MAC). This process ruptures target cell membranes and leads to cell lysis, achieving cytotoxic effects on the target cells. Researchers assess the binding capacity of therapeutic antibodies with C1q through the C1q binding assay, determining the antibody's effectiveness in the immune response.

Researchers have surmounted numerous challenges in disease treatment through advanced techniques such as the C1q binding Assay and ADCP assay. In cancer treatment, scientists have successfully developed a series of antibodies targeting specific antigens. These drugs activate immune cells, propelling them to engulf and annihilate cancer cells. The successful application of this immunotherapy brings renewed hope to tumor treatment.

In the domain of autoimmune disease treatment, researchers are leveraging antibodies to target diseases resulting from immune system overactivation. Through meticulous C1q binding assay studies, scientists can pinpoint the most suitable antibodies for treatment, precisely modulating the immune system's activity to achieve therapeutic goals.

Moreover, in the realm of treating viral and bacterial infections, the utilization of the ADCP assay is on the rise. Researchers have formulated a series of antibodies targeting pathogens, effectively eliminating infection sources by stimulating immune cells to engulf these pathogens. Consequently, this approach has significantly heightened the success rate of infectious disease treatments.

With the continuous evolution of single-cell technologies and CRISPR gene editing techniques, researchers can delve deeper into cell death mechanisms, antibody structures, and immune cell functions. This progress will further accelerate research on ADCC enhancement, offering more precise and efficient means for disease treatment.

The realm of biopharmaceuticals plays a crucial role in modern medical treatment, yet faces significant challenges. A notable concern is the brief half-life of many biopharmaceutical products, leading to swift degradation and clearance from the patient's body, necessitating frequent dosing. This article delves into the ways in which half-life extension strategies in drug development can effectively tackle this issue, enhancing patient convenience and optimizing therapeutic outcomes.

Biopharmaceuticals encompass a diverse array of drugs derived from endogenous peptides and proteins, spanning hormones, enzymes, growth factors, interferons, and antibodies. Despite their immense therapeutic potential, a common drawback is the short half-life of most therapeutic proteins, often lasting mere minutes to a few hours. This necessitates frequent administration, posing challenges for patients and potentially exacerbating symptoms if doses are missed. Extending the plasma half-life of these drugs holds the key to prolonging dosing intervals, easing patient burden, and elevating their overall quality of life, especially for those with chronic diseases requiring lifelong treatment.

Several strategies contribute to the extension of drug half-life in the realm of drug discovery and development. These include polymer conjugation, bioactive natural protein conjugation, carbohydrate modification, and sustained-release drug delivery systems.

Bioactive natural protein conjugation, gaining popularity due to reduced toxicity, includes well-established technologies such as albumin conjugation. This technique is widely employed in numerous protein drugs available in the market. The Fc-Fusion technology, applicable to various therapeutic proteins, has shown positive effects on half-life extension, therapeutic efficacy, and physical properties.

The Fc fusion strategy entails utilizing the Fc portion of immunoglobulin G (IgG) molecules to prolong the circulating time and bioavailability of biopharmaceutical products. Analytical tools are essential for characterizing these structurally complex and heterogeneous Fc fusion proteins, confirming primary structure, assessing post-translational modifications, and evaluating physicochemical attributes.

Sustained-release drug delivery systems aim to extend a drug's presence in the body by controlling its release rate. This is achieved through encapsulating the drug within carriers, such as particles, films, and gels. Nanoparticle-based systems and lipid-based systems play pivotal roles in modulating the pharmacokinetics and pharmacodynamics of therapeutic agents, gradually releasing the drug into circulation and protecting it from enzymatic hydrolysis.

By controlling drug release rates and leveraging the stability of the Fc portion, these innovative strategies offer promising avenues for extending drug half-life, enhancing therapeutic efficacy, and improving the overall drug administration experience for patients. These advancements mark significant progress in the biopharmaceutical field, providing patients with more durable, convenient, and effective treatment options for the future.

Antibodies, the extraordinary proteins that serve as the frontline troops of the human immune system, have recently gained attention for their ability to combat tiny compounds known as haptens. Because of their small size, these elusive targets present particular difficulty for the immune system to identify as foreign invaders. However, researchers' inventiveness has resulted in the creation of several techniques to bypass this barrier and unleash the full potential of hapten antibodies.

The search for hapten antibodies has been accompanied by a slew of novel techniques, injecting a burst of creativity into the field. To increase immunogenicity, one technique involves connecting haptens to bigger carrier molecules such as proteins or polymeric materials. Adjuvants, which operate as immune system enhancers, are another strategy used to stimulate a more robust response. Furthermore, anti-hapten antibodies, a subset of antibodies that recognize and bind to haptens, have emerged as a potent tool in the search for hapten-specific antibodies.

Hapten-specific antibodies offer a wide range of uses, ranging from biotechnology to diagnostics and therapies. One of the most interesting areas is the development of small-molecule antibody therapies, a new class of antibodies designed to target and neutralize disease-causing small-molecules. These small-molecule antibodies have distinct advantages over standard small-molecule medications, including increased specificity and affinity for their targets, which reduces the likelihood of off-target effects and increases efficacy.

With the growing demand for small-molecule antibody therapies, specialist services that offer custom antibody generation against a wide range of small compounds have emerged. Creative Biolabs is a US-based biotech company that specializes in small-molecule antibody design and development and can provide a series of services related to small-molecule antibodies. These services use a potent combination of immunization and screening approaches to create antibodies with exceptional specificity and affinity for the target. The resulting antibodies can then be fine-tuned for a wide range of applications, from in vitro diagnostics to therapeutic treatments, opening up a world of possibilities for researchers.

Finally, the development of hapten-specific antibodies has sparked a surge of innovation in the fields of small-molecule antibody therapies and diagnostics, holding enormous potential for the detection and treatment of a wide range of disorders. Access to these cutting-edge tools has been democratized by the availability of specialist small-molecule antibody development services, allowing researchers and enterprises to adapt antibodies to their unique needs. As the research progresses, the potential for small-molecule antibodies to make even larger strides in the near future grows.

Cancer has been a leading cause of death worldwide for decades, accounting for nearly one in every six deaths and posing a serious threat to people's health. A great number of plans and approaches have been approved to support the improvement of cancer cure rates with ongoing research on cancer treatment.

A recent study demonstrated that γδ T-cells were found to be the most prognostically beneficial immune cell subset in tumor infiltrates from 18,000 tumors across 39 malignancies, which makes γδ T-cells a kind of highly promising effector cell compartment for cancer immunotherapy. At present, γδ T cells have indicated powerful anti-tumor efficacy against breast cancer, colon cancer, lung cancer, leukemia, and others.

As innate immune cells, indeed, gamma delta T cells can recognize tumor cells independently of human leukocyte antigen (HLA) restriction and quickly produce abundant cytokines and potent cytotoxicity in response to malignancies. Gamma delta T cells have several favorable features for the development of T cell-based therapy for cancer, which are listed below:
* Gamma delta T cells recognize a broad spectrum of antigens on various cancer cells.
* Gamma delta T cells recognize their target cells independent of the major histocompatibility complex (MHC).
* Gamma delta T cells are distributed in various tissues and can quickly respond to target tumor cells.
* Gamma delta T cells interact with other immune cells such as B cells to drive a cascade of immune responses against tumors.

Isolating and purifying functional and specific gamma delta T cell populations from a complex biological sample is crucial for understanding the biological function of gamma delta T cells and creating gamma delta T cell-based therapies. Therefore, outstanding technologies for T cell isolation play a critical role. Magnetic bead cell sorting (MACS) is a frequent, efficient, and quick method for isolating uncontaminated gamma delta T lymphocytes from human peripheral blood mononuclear cells (PBMCs).

In addition, due to the essential function of gamma delta T cells in several diseases, a T cell cytotoxicity test is necessary for testing gamma delta T cell activity and cytotoxicity. The normal cytotoxicity tests include the LDH cytotoxicity test, flow cytometry-based cytotoxicity test, and impedance-based label-free real-time cytotoxicity assay, in which the LDH cytotoxicity test is one of the most commonly used methods for cell cytotoxicity detection.

Creative Biolabs is a biotechnology business that focuses on the discovery of gamma delta T cells to combat human cancers. They established and optimized robust platforms in-house for the selective isolation and expansion of anticancer gamma delta T cell populations from human tissues. Furthermore, they offer preclinical research services to assess the safety and efficacy of gamma delta T cell-based cancer immunotherapy.