Immune-Stimulating Antibody Conjugation (ISAC)

Our professional ISAC services focus on addressing cancer immunotherapy research obstacles. Immunostimulating antibody conjugates represent a novel type of therapeutic antibody-drug conjugates that trigger both innate and adaptive immune responses to achieve dual effects in eradicating tumor cells. Many immunostimulating antibody conjugates remain in clinical development's preliminary phase or have not succeeded in clinical trials. The development of improved immunostimulating antibody conjugates that address their current limitations including high toxicity levels strong immunogenic responses extended development durations and subpar pharmacokinetic attributes is essential. We provide solutions that enable you to surmount these difficulties while speeding up your research activities.

What is ISAC?

ISAC consists of three main components: tumor targeting antibodies, non degradable linkers, and proprietary immune stimulants for activating the innate immune system. ISAC can activate and recruit bone marrow cells through targeting a single marker on the tumor cells to produce a new immune response. Through releasing cytokines and chemokines, attracting related immune cells and reducing the activation threshold of immune response, bone marrow cells which are activated begin the feedforward cycle. This will reprogram the tumor microenvironment, and then trigger an immune response which can be adaptive against the tumor, so as to provide a lasting response for patients.

Function of ISAC

ISAC is similar to undercover entering tumors to activate innate immunity and inform external immune cells at the same time. The following table lists the three functions and their roles of ISAC.

Table 1 Three functions and their roles of ISAC

Immunostimulating Antibody Conjugate Services

Antibody-TLR Agonist Conjugates: TLR agonists demonstrate strong tumor fighting abilities that make them effective as standalone treatments or when combined with additional therapies. These agents serve as vaccine adjuvants by activating both innate and adaptive immune responses while altering the tumor microenvironment and enhancing T-cell function.

Antibody-STING Agonist Conjugates: Researchers have discovered and developed multiple natural and synthetic STING agonists which have been tested in preclinical models and clinical trials for cancer and infectious disease immunotherapies. These agonists trigger immune responses.

Antibody-Chemokine Conjugates: Chemokines function in two different ways during tumor formation. They function as adjuvants to recruit immune cells to tumors yet also participate in tumor survival and metastasis development while promoting angiogenesis. The antibody part of antibody-chemokine fusion methods directs chemokines to tumors where they boost immune cell penetration.

Antibody-ImmunoCheckpoint Inhibitor Conjugates: PD-1 and CTLA-4 demonstrate successful cancer treatment outcomes through ImmunoCheckpoint inhibitors yet cause serious adverse effects when administered systemically. The combination of checkpoint inhibitors with tumor-specific antibodies allows targeted delivery which minimizes normal tissue impact and strengthens antitumor effects.

Antibody-Cytokine Conjugates: IL-2 and IFN-γ cytokines hold essential roles in controlling immune system functions. When cytokines are attached to antibodies they reach tumor locations directly which boosts immune responses at these sites and decreases systemic toxicity.

Antibody-Immunotoxin Conjugates: Immunotoxins target tumor cells for destruction by linking cytotoxic molecules to antibodies. Through optimization of conjugation techniques researchers can enhance both stability and effectiveness of immunotoxins while minimizing their immunogenic response.

Our Development Process

1. Consultation and Needs Analysis: Our technical team will communicate with you in-depth to understand your specific needs, including target antigens, types of immunostimulants, expected therapeutic effects, etc., to provide you with personalized solutions.
2. Antibody Selection and Design: Based on your needs, we will select the most suitable tumor-targeting monoclonal antibody from a broad antibody library and make necessary modifications to enhance stability and specificity.
3. Immunostimulant Selection and Optimization: We offer a variety of immunostimulants such as TLR agonists, STING agonists, and chemokines. Our scientists will select the most suitable immunostimulant based on your project requirements and optimize it for improved activity and stability.
4. Conjugation and Purification: Under strict aseptic conditions, we will carry out the conjugation reaction between antibodies and immunostimulants. By optimizing conjugation conditions, we ensure that the optimal number of immunostimulants is attached to each antibody molecule for maximum therapeutic effect. After the reaction, we will use advanced purification techniques such as size-exclusion chromatography (SEC) and high-performance liquid chromatography (HPLC) to remove unbound immunostimulants and other impurities, ensuring the purity and quality of the final product.
5. Quality Control and Verification: We conduct comprehensive quality control of the conjugate products, including physicochemical property analysis, biological activity validation, and stability testing. Using advanced instruments and techniques such as flow cytometry, enzyme-linked immunosorbent assays (ELISA), and cell culture, we ensure that the conjugate products meet your requirements.
6. Delivery and Follow-up Support: After completing all quality control steps, we will package and ship the products according to your specifications to ensure safe delivery to your laboratory. Additionally, we provide comprehensive follow-up technical support, including experimental guidance, data interpretation, and troubleshooting, to ensure smooth progress in your research.

Why Choose Us?

Rich Experience and Expertise: Our team has years of experience in the field of immunostimulating antibody conjugates and has a deep understanding of the challenges and opportunities in this area. We possess solid knowledge in immunology, oncology, and medicinal chemistry, enabling us to provide scientifically sound design solutions and technical support.

Advanced Technological Platform: We are equipped with world-leading technology and equipment, such as high-precision flow cytometers, advanced conjugation equipment, and efficient purification systems, ensuring the efficiency of the conjugation process and the high quality of the products.

Rigorous Quality Control System: We follow strict quality control standards, from raw material sourcing to final product delivery. Every stage is carefully monitored and validated. We ensure that the immunostimulating antibody conjugates we provide are of high purity, high activity, and good stability to meet your research needs.

Customized Service: We understand that every research project has its unique requirements, so we offer personalized service plans. Whether you are conducting basic research or preclinical studies, we can tailor the most suitable immunostimulating antibody conjugates based on your specific needs.

Fast and Efficient Delivery Cycle: We know that time is crucial for research projects, so we are committed to optimizing service processes and improving work efficiency. While ensuring product quality, we can complete your order quickly, ensuring that you receive the immunostimulating antibody conjugates you need in a timely manner, accelerating your research progress.

Our Technology

Antibody-Immunostimulant Conjugation Technology: We use advanced conjugation techniques to ensure stable connection between antibodies and immunostimulants. Our conjugation methods are efficient, highly specific, and do not affect antibody activity, allowing us to produce high-quality immunostimulating antibody conjugates.

Bioconjugation Chemistry Optimization Platform: Our team of scientists is proficient in various bioconjugation techniques and can optimize the conjugation process. By adjusting conjugation conditions, selecting suitable linkers, and optimizing reaction systems, we can increase conjugation efficiency, reduce impurity levels, and ensure that the final product achieves optimal performance.

Quality Analysis and Control Platform: We are equipped with comprehensive quality analysis instruments and techniques, such as high-performance liquid chromatography (HPLC), mass spectrometry (MS), and flow cytometry (FACS), to perform comprehensive quality analysis and control of immunostimulating antibody conjugates. We strictly adhere to quality standards to ensure that each batch of products meets the required specifications.

Application of ISAC

ISAC has achieved complete tumor regression and lasting anti-tumor immunity in a variety of tumor models. ISAC plays its role mainly by coupling tumor targeted monoclonal antibodies with immune agonists through non cleavable linkers. Studies have reported that APCs can be activated and induced to mature in vitro through the effect of rituximab T785-ISAC. The functional Fc fragments of TLR agonists and antibodies play vital role in activating APCs, indicating the significance of FcγR in the absorption and internalization of ISAC. The activation of APCs can be induced by ISAC through the joint action of FcγR and TLR. ISAC enhances the function of anti-tumor myeloid cells through the synergistic activity of two signal pathways. In addition, by inducing a strong pro-inflammatory environment, ISAC could accumulate activated myeloid APCs and increase the number of local cytokines and chemokines. Studies also have found the cured mice were further protected when re-implanted into the tumor, indicating that ISAC has a significant anti-refractory large tumor effect in the presence of B cells, T cells and NK cells.^[1]

Fig.1 Graphical depiction of the two-step T785-ISAC conjugation reaction.

Cancer Immunotherapy: Immunostimulating antibody conjugates, as a new cancer treatment approach, have broad prospects. They can deliver immunostimulants directly to the tumor site, activate immune cells in the tumor microenvironment, and enhance the body's immune response to the tumor, thereby more effectively clearing tumor cells. In various cancer models, immunostimulating antibody conjugates have demonstrated significant antitumor effects, offering new hope for cancer treatment.

Tumor Microenvironment Regulation: The tumor microenvironment plays a critical role in tumor initiation, progression, and metastasis. Immunostimulating antibody conjugates can regulate the composition and function of immune cells in the tumor microenvironment, break immune suppression, and promote the generation of antitumor immune responses. For example, they can attract more dendritic cells, macrophages, and T cells into the tumor microenvironment to enhance immune surveillance and cytotoxicity.

Vaccine Adjuvant Development: Immunostimulating antibody conjugates can also serve as vaccine adjuvants when combined with tumor antigens to improve the immunogenicity and therapeutic effects of vaccines. They can activate the innate immune system, enhance the function of antigen-presenting cells, promote T-cell activation and proliferation, thereby triggering stronger specific immune responses and improving the preventive and therapeutic effects of vaccines against tumors.

Immunology Research: Immunostimulating antibody conjugates provide a powerful tool for studying immune system functions and mechanisms. By examining their interactions with immune cells, we can gain deeper insights into the mechanisms of immunostimulants in immune responses and the effects of antibody-mediated targeted delivery on immune regulation. This research helps uncover the mysteries of the immune system and provides a theoretical basis for developing new immunotherapies.

Frequently Asked Questions (FAQ)

1. How do you ensure the quality of immunostimulating antibody conjugates?

We have a strict quality control system in place, carefully monitoring and validating every step, from raw material selection to final product testing. We use advanced instruments and techniques to comprehensively analyze the physicochemical properties, biological activity, and stability of the conjugate products, ensuring their quality meets your requirements. Additionally, we provide detailed quality reports, including key indicators such as purity, activity, and endotoxin levels, so you have a clear understanding of the product’s quality.

2. Do you offer customized immunostimulating antibody conjugate services?

Yes, we offer comprehensive customized services. Whether you need specific antibodies, immunostimulants, or have special design requirements, we can tailor the most suitable immunostimulating antibody conjugates based on your needs. Our technical team will work closely with you to provide personalized solutions, ensuring that the final product best meets your research goals.