Earlier today, Seattle Genetics Inc, announced the initiation of a new Phase I clinical trial of SEA-CD40, which utilizes the company’s proprietary Sugar-Engineered Antibody technology or SEA designed to target CD40 and stimulate the immune system used for the treatment of multiple types of advanced solid tumors.

SEA-CD40 targets CD40, a widely expressed stimulatory receptor found on antigen-presenting cells or APCs which play a role in immune cell activation. Preclinical data show that SEA-CD40, the first clinical antibody employing Seattle Genetics’ technology,  stimulates the immune system to fight cancer. This technology is complementary to the the company’s antibody-drug conjugates (ADC) technology.

Non-fucosylated monoclonal antibodies
SEA technology increases the potency of monoclonal antibodies by producing a non-fucosylated monoclonal antibody, resulting in an enhanced innate immune response. 

Research has shown that non-fucosylated therapeutic monoclonal antibodies show a more potent efficacy than their fucosylated counterparts both in vitro and in vivo.  Furthermore, non-fucosylated therapeutic monoclonal antibodies are not likely to be immunogenic because their carbohydrate structures are a normal component of natural human serum IgG. As a result, the application of non-fucosylated antibodies is expected to be a powerful and elegant approach to the design of the next generation therapeutic antibodies with improved efficacy.[1][2]

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Enhanced binding to effector cells results in better crosslinking and activation of CD40 signaling in immune cells. This stimulation of the patient’s own immune cells has the potential to result in antitumor activity. Preclinical studies show that the non-fucosylated antibody is a potent stimulator of immune cells that may be able to harness the power of a patients’ immune system to fight cancer.

Simpler and more cost-effective
A unique key feature of Seattle Genetics’ SEA technology is that genetic modification of the antibody-producing cell line is not necessary and standard cell culture conditions can be used, while maintaining the underlying manufacturing processes, yields and product quality. As a result, researchers at Seattle Genetics believe that the SEA approach is much simpler and more cost-effective to implement as compared to existing technologies for enhancing antibody effector function, most of which require development of new cell lines.

Clinical trial
The study is a phase I, open-label, multi-center, dose-escalation clinical trial of SEA-CD40 in patients with advanced solid tumors who have failed current standard of care treatments. Expansion cohorts are planned to evaluate SEA-CD40 across up to three cancer indications that will be determined based on data from the dose escalation portion of the study. The primary endpoints are determination of the maximum tolerated dose or MTD and safety profile of SEA-CD40.

In addition, the researchers will evaluate antitumor activity, pharmacokinetics and immunological pharmacodynamic effects. The phase I trial will enroll approximately 50 patients during dose escalation and up to 90 patients in the expansion cohorts at multiple centers in the United States.

Commenting on the initiation of the trial, Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics, said: “We are pleased to advance our SEA-CD40 immuno-oncology program into the clinic to evaluate it broadly in multiple types of solid tumors. Our proprietary SEA technology builds on our expertise in empowered, targeted approaches for the treatment of cancer and represents a novel technology designed to increase the potency of monoclonal antibodies through glycoengineering which may lead to an improved antitumor immune response. We look forward to data from the phase I trial.”

Preclinical findings with SEA-CD40 will be presented at the upcoming American Association for Cancer Research (AACR) annual meeting which will be held in Philadelphia, April 18 – 22, 2015.

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