March 15, 2016 (Vol. 36, No. 6)
Immuno-PET Imaging Detects Radiolabeled Minibodies That Light Up CD8 T Cells
Any immune therapy, however promising it may seem at the outset, will fail unless it stimulates an adequate immune response. But even a failure can be instructive—provided it is detected quickly enough. For example, if the response to immuno-oncology can be gauged in timely fashion, physicians have the chance to rethink their treatment strategies, without even having to wait until changes in tumor size are detected. Similarly, drug developers may seize the opportunity to determine whether their immune modulators work well enough to justify further investment.
In hopes of providing timely immune response information, ImaginAb has developed an immune-imaging platform that provides whole-body pictures. The ImaginAb platform and its proprietary imaging agents fill a great unmet need, says Benjamin Chen, Ph.D., ImaginAb’s newly appointed CEO. “Only one-third to one-half of patients receiving immuno-oncologic therapies respond,” Dr. Chen points out. He adds that knowing whether a treatment is working soon after it is administered can save precious time and resources.
ImaginAb’s immune imaging technology is used in conjunction with positron emission tomography (PET). The overall approach is something ImaginAb refers to as immuno-PET.
According to ImaginAb, the imaging platform lets physicians noninvasively test patients soon after the start of treatment, and it allows visualization of a patient’s response to the treatment within a few days, revealing the exact locations and extent of tumors. Traditional imaging methods, with their limited sensitivity, can’t deliver such information until six to eight months after treatment begins, when the tumor size increases, decreases, or has no change.
The platform combines a proprietary protein armed with a radioactive tracer. With immuno-PET imaging, says Dr. Chen, the agent “lights up,” enabling physicians to identify specific CD8 T cells around tumors. “If there are lots of those cells,” Dr. Chen advises, “administer the immunotherapy.”
Dr. Chen suggests that something like the immuno-PET platform would have been useful during a recent (and prominent) instance of immunotherapy: “When former U.S. President Jimmy Carter underwent immunotherapy for cancer in the brain, the therapy worked. We don’t know why. There really were no biomarkers to check, and biopsies were out of the question.”
By highlighting the CD8 T cells surrounding tumors, the ImaginAb platform overcomes those obstacles. Physicians, therefore, can determine who is most likely to benefit from specific treatment and whether a treatment is working for a given individual.
89Zr-Df-IAB22M2C, ImaginAb’s lead imaging compound, is a radiolabeled monoclonal antibody fragment known as a minibody. The minibody maintains the specificity of full-length antibodies but has no immune effector functions and is, therefore, inert.
Dr. Chen explains that the molecule is nonglycosylated to minimize protein heterogeneity and potential side-effects associated with intact antibodies: “This imaging agent clears within three days, enabling repetitive testing.” The molecules also bind with high affinity and penetrate the tumor more deeply that other imaging agents.
At this point, the immuno-PET platform detects only CD8 T cells. Versions are being developed to detect CD4 cells and other immune cell targets. Its immuno-oncology molecule, IAB22M2C, is at the preclinical stage before beginning human trials later in 2016.
Better Than CT Scans
“In prostate cancer, physicians often are looking at the wrong biomarkers,” Dr. Chen says. And in glioblastoma, there are no biomarkers. To address this need, ImaginAb has developed 89Zr-Df-IAB2M to detect the target prostate-specific membrane antigen on the surface of cancer cells.
Dr. Chen asserts that when data from this approach was compared to the gold standard for prostate cancer, the ImaginAb approach identified more tumors with fewer false positives. “This was verified by pathology results,” insists Dr. Chen. “That’s the power of our platform.”
Specifically, the Phase I/IIa study of 89Zr-Df-IAB2M with PET imaging detected 85% of the bone lesions, compared to 51% for CT scans and 52% for bone scintigraphy. For soft-tissue lesions, 89Zr-Df-IAB2M detected 82% of the lesions, compared to 57% for CT scans. All IAB2M results were true positives or negatives, according to ImaginAb data.
The IAB2M program for prostate cancer is in Phase II trials. In time, the company also plans to enter the anti-androgen space to detect early-stage disease.
Immuno-PET and subsequent versions of this platform have obvious value for physicians seeking to direct patient therapies, but it also has significant value for drug developers. “For immunomodulators, for example, the need is huge,” Dr. Chen observes.
Small molecule drugs can be evaluated in a Petri dish, Dr. Chen continues, but immunomodulator behavior in a Petri dish may not represent immunomodulator behavior inside the human body. Instead, researchers need to actually see the effects of their therapeutics in a biological system. According to Dr. Chen, the ImaginAb platform provides that view, thus informing researchers’ patient management decisions.
ImaginAb is building out its pipeline and plans to launch additional clinical trials, with read-outs expected third quarter 2016. The company also cites the importance of Japan in its development plans. At present, ImaginAb has a small presence in this very important market, but this presence could expand. “A number of strategic partners in Japan are interested in what we’re doing,” confides Dr. Chen.
The company also is boosting its internal expertise. It recently added two industry veterans to its board of directors and formed a medical advisory board. At the same time, ImaginAb is recruiting partners to help shape the next generation of immunotherapy, to increase the options for drug developers, physicians, and patients.
Location: 423 Hindry Avenue, Unit D, Inglewood, CA 90301
Phone: (310) 645-1211
Principal: Benjamin Chen, Ph.D., CEO
Number of Employees: 25
Focus: ImaginAb aims to improve patient care through noninvasive precision imaging. The company uses minibodies, radiolabeled monoclonal antibody fragments, to illuminate high-value molecular targets that couldn’t be imaged previously.