A variety of different imaging approaches, spanning molecular to whole-body scans, have contributed greatly to our understanding of the conditions required for an effective anticancer immune response, reports Ian Wilson, CEO, ImaginAb
Immunotherapy has shown promising outcomes in multiple cancer types. The US Food and Drug Administration and European Medicines Agency have approved several immunotherapeutic drugs, including checkpoint inhibitors, which have been fully accepted in clinical practice.
Complementary to these therapies, antibody based positron emission tomography (known as immuno-PET imaging) has become an increasingly important way to visualise and characterise tumour lesions.
Antibody imaging for immunotherapy can visualise systemic drug distribution as well as provide insight regarding the localisation of the drug inside the tumour. In vivo imaging in preclinical models has been instrumental in understanding the complex interactions of cancer and the immune system.
The great task now lies in imaging immune responses in real cancer patients in a safe and non-invasive manner to realise the full potential of immunotherapy in the clinic. Additionally, imaging can be used to identify patients who may benefit from a particular therapy and predict and monitor its outcome. In recent years, the field has focused on zirconium (89Zr), a radiometal with near-ideal physical and chemical properties for immuno-PET.
To date, 89Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown how 89Zr-based immuno-PET can be used to tailor treatment for individual patients.
Although radiolabelled antibodies are an excellent choice for non-invasive imaging and for monitoring changes of target antigens with time, they have limitations — a major one being the long blood clearance required, which means it usually takes 3–5 days after injection before an accurate image can be obtained.
Some companies are leading the way in providing solutions to these challenges. Clinical stage immuno-oncology imaging company ImaginAb has developed a “minibody” technology platform to be used in whole body in vivo imaging. This minibody is designed and manufactured in such a way that allows same-day imaging, while maintaining the specificity and sensitivity to quantitatively assess the immunological status of each cancer lesion within a patient.
The platform’s lead product is 89ZrCD8PET. Owing to the half-life of 89Zr, patients can be imaged for up to six days with the minibody imaging agent, allowing early changes in therapy to be measured. Another positive aspect of this approach is that 89Zr can be imagined using current existing infrastructure and does not require modification of pre-established imaging systems.
In the context of tumour immunology, it has become apparent that within the tumour micro-environment, CD8 tumour infiltrating lymphocytes are an important component in eliciting a therapy response and are linked to disease outcome.
Although immunotherapies are successful, they only work in a subset of patients.
Therefore, the ability to determine the immune response post therapy in a non-invasive way is crucial in the clinical decision of advising appropriate treatment. 89ZrCD8PET allows the full body visualisation of the CD8 cells distribution, both in normal and tumour tissue. Data from studies highlight the potential of 89ZrCD8PET to address fundamental questions regarding the role of CD8 cells in the fight against cancer.
This agent can also replace the need for biopsy and allow early, quantitative, whole-body pharmacodynamic readout of developmental drug efficacy improving internal pharma decision making on which new immunotherapies and/or combination treatments to progress in R&D.
In fact, a number of pharma companies, including Boehringer Ingelheim, Merck, Nektar and Roche, plan to employ this 89ZrCD8PET imaging agent imaging in clinical trials to explore the efficacy of novel immune-oncology therapies. For many pharma companies, this technology provides an important new tool to improve clinical development of next generation immunotherapies by improving patient selection and stratification. It provides an opportunity to see early efficacy data derived from new drug treatments.
In summary, 89ZrCD8PET is rapidly advancing as a key technology in immuno-oncology clinical trials. It has the potential to be translated into full clinical practice owing to its exquisite specificity, sensitivity and easier manufacturing logistics compared with other shorter half-life isotope imaging agents.