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New Vaccine Has the Potential To Treat Several Different Cancers

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Researchers recently reported in Clinical & Translational Immunology the development of a novel cancer vaccine. The vaccine is designed to target malignancies that express the transcription factor Wilms' tumor 1 (WT1) – a well characterized and highly immunogenic tumor‐associated antigen. As WT1 is overexpressed in several hematological and solid malignancies, the vaccine has the potential to treat many different cancers.

Technology Networks
had the pleasure of speaking with the project’s lead researcher, Associate Professor Kristen Radford to learn more about the CLEC9A-WT1 vaccine, how it works and the key advantages it offers compared to existing cancer vaccines.

Laura Lansdowne (LL): Could you tell us more about your area of expertise and the work you do at The Translational Research Institute?

Kristen Radford (KR):
I lead the Cancer Immunotherapies Research Group at the Mater Research Institute that is based at The Translational Research Institute in Brisbane, Australia. We work on a special type of white blood cell called a dendritic cell. Dendritic cells train the immune system to mount responses against pathogens and cancer. Our work is focused on understanding the role of human dendritic cells in health and disease and we are using this knowledge to develop new treatments for cancer and other diseases. We have been developing new vaccines that harness the power of dendritic cells to train the immune system to recognize and fight cancer.

LL: What is the transcription factor Wilms' tumor 1 (WT1) and what makes it such an attractive therapeutic target for cancer?

WT1 acts as an oncogene that promotes tumor growth and development. It is highly expressed by many different cancer types including most types of blood cancer and many solid cancers but is not expressed by healthy tissues. Importantly it is highly immunogenic, that is, killer T cells within the immune system can recognize it and kill cancer cells that express it while sparing healthy tissues that don’t.

LL: The Translational Research Institute recently issued a
press release summarizing your work in relation to developing a cancer vaccine. Could you tell us more about the study, the design of the vaccine, and the cancers it is intended to treat?

Dendritic cells are comprised of several subtypes that each direct highly specialized immune responses. Our previous research had identified the key human dendritic cell type responsible for inducing tumor immune responses. This subtype exclusively expresses a molecule call CLEC9A, that plays an important role in processing proteins such as WT1 into a format that can be recognized by, and activate, cancer-specific killer T cells. Our vaccine, called CLEC9A-WT1, is an antibody specific for CLEC9A that acts as a guided missile to specifically deliver WT1 to the key dendritic cell subset responsible for initiating cancer-specific immune responses. Our CLEC9A-WT1 vaccine was more effective at activating killer T cells than other vaccines in preclinical laboratory models. It is intended to treat WT1 expressing cancers, which include leukemias as well as many solid cancers including ovarian cancer. This vaccine was developed in collaboration with Associate Professor Mireille Lahoud from Monash University, Melbourne and made possible with funding from Worldwide Cancer Research UK and the Mater Foundation in Brisbane.

LL: You mention that the CLEC9A‐WT1 vaccine offers several key advantages over existing cancer vaccines – could you elaborate on these?

Many cancer vaccines are made from a type of dendritic cell derived from the patient’s own blood. In addition to the practicalities and expense of these patient-specific dendritic cell therapies, this type of dendritic cell is not optimal for inducing tumor immune responses. Other vaccines are not made with patient cells and do not specifically target dendritic cells, making them less effective and prone to off-target side effects. Our vaccine avoids the requirement for taking patient blood, making it an “off-the-shelf” product that is more practical and cost-effective to produce as well as more suitable for treating a wider range of patients. Additionally, because our vaccine delivers WT1 specifically to the CLEC9A-expressing dendritic cell subset responsible for inducing cancer immune responses it is likely to be more effective as well as reducing potential for side effects.

LL: Could you comment on next steps, in terms of additional preclinical studies and the prospect of clinical studies?

We are making some minor refinements to the vaccine as additional safety features. We now require funding to make and validate a clinical-grade version and hope to have clinical studies underway within the next three years.

Kristen Radford was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.