Our clinical protocols incorporate knowledge from our immunomonitoring program to determine the type of product and it’s optimal route and frequency of dosing in order to elicit a desired immune cascade toward elimination of a threat. In this manner, the power of our products in controlling the immune system is expanded by integrating knowledge of immune mechanisms into the design and use of the products.
In order to obtain new information on the immune effects of our products and the immune status of our patient volunteers, we design immunomonitoring points at critical points in each protocol. At these critical points, we sample blood and tissue. Measuring multiple immune parameters in blood and tissue is expected to help us to better map the cascade of immune events that occur in responding patients. In the case where a patient does not respond, immunomonitoring may also provide information as to the point in the immune cascade that didn’t not occur correctly. In addition, our immunomonitoring programs seeks to find surrogate biomarkers that might serve to predict the patients with an immune profile most likely to respond.
Knowledge that an immune cascade has occurred correctly can also provide helpful information to a treating oncologist trying to determine whether a patient is responding or progressing after immunotherapy. This is important, as, for example in cancer, current methods of measuring response to therapy were developed for chemotherapy are not applicable to immunotherapy. For chemotherapy, the methods are focused on the ability to cause the tumor to shrink or to reduce the overall tumor burden. Measure of the size and number of tumor lesions using imaging techniques, such as CT scan or PET scan, before and after chemotherapy provides an indication of whether the chemotherapy was effective. Effective chemotherapy regimens will have a rapid effect on reducing the number and sizes of tumor lesions.
However, effective immunotherapy often causes tumors to swell and appear larger of CT scan. In addition, new lesions that might have been too small to see on CT scan before immunotherapy may become visible after immunotherapy making it appear as if the tumor has spread. In addition, for reasons not fully understood, some patients progress for months before they respond to immunotherapy. Some patients after immunotherapy will remain with large tumor burdens but will not develop any new lesions. Many of these patients live long without any additional therapy. The tumors and the immune system reach a level of balance. The radiologist may interpret a scan from such a patient as ‘no response’ because the tumor size didn’t change or actually got a little larger. However, many patients with stable disease after immunotherapy are able to live long, productive lives.
The immune response occurs as a cascade of events in space and time in a network setting. Analysis of a single event in the cascade at a single point in time may not be representative of the whole cascade of events. A single parameter may be high one day and low another day. If in a disease state, we only measured once on the high day, we may erroneously decide that developing a drug to lower this parameter will solve the problem and enable the immune system to eliminate the disease. However, such a narrow view of the immune system could cause undesired effects or the disturbance of the parameter could simply be corrected by the immune system resulting in no effect. We understand the immune system to work as a dynamic network with the ability to learn. We believe that immunotherapy must be able to either unravel immune networks which failed in order to protect against disease, or must teach the system new effective immune networks that imprint over, and disable, the existing failed network. In order to accomplish this, we must sample multiple parameters at multiple times at key points in the immune cascade.
We design into all our clinical protocols immunomonitoring end-points. We collect both blood and tissue (biopsy) samples before, after, and at strategic times during, our immunotherapy protocols. We also schedule imaging studies (e.g. CT scan) at the same time as biopsy samples are taken in order to better understand how to interpret the images of patients that have undergone immunotherapy.