Science and medical researchDCVax® is a platform technology that uses activated dendritic cells (the master cells of the immune system), and is designed to reinvigorate and educate the immune system to attack cancers. Unlike conventional cancer drugs, which use one active agent to hit one target on the cancer, DCVax uses many active agents to hit many targets on the cancer.

We believe that at least three key aspects of the DCVax technology contribute to the positive results (described more fully below) seen in clinical trials to date:

(1) DCVax is designed to mobilize the entire immune system, not just one among the many different categories of immune agents in that overall system.

As described above, DCVax is comprised of activated, educated dendritic cells, and dendritic cells are the master cells of the immune system, that mobilize or help the entire immune system. Some of the prominent cancer drugs today are composed of just one type of antibody — and antibodies themselves are just one type of agent in the overall immune system “army” (see Diagram 1 above). In contrast, the full immune system involves many types of antibodies, and also many other kinds of agents besides antibodies. Similarly, there have been a variety of early immune therapies that failed in the past. These, too, typically involved single agents, such as a single one among the many, many types of immune signaling molecules (e.g., a particular interferon or interleukin), or a single type of agent such as T cells alone, etc. In contrast, dendritic cells mobilize all of these different categories of agents, comprising the whole immune system “army,” in combination with each other and in their natural relationships to each other.

(2) DCVax is designed to target not just one but the full set of biomarkers on the patient’s tumor.

As mentioned above, cancer drugs are typically rifle shots aimed at just one target on a patient’s cancer. However, cancer is a complex and variable disease. Tumor profiles vary among patients with the “same” cancer and also vary as the disease progresses. Further, when rifle shot drugs hit individual targets on cancers, the cancers find ways around them (called “escape variants”) — and the rifle shot treatments then usually stop working. DCVax takes the opposite approach: instead of aiming at a single target, DCVax is designed at to target the full set of biomarkers on a patient’s cancer. Such a treatment approach is expected to make it more difficult for tumors to develop escape variants.

(3) DCVax is personalized, and targets the particular biomarkers expressed on that patient’s tumor.

Extensive scientific evidence has shown that there is substantial variation in tumor profiles and characteristics among patients with the “same” cancer. The degree of variation is particularly enormous in some of the most aggressive cancers, such as GBM brain cancer and pancreatic cancer. Cancer drugs are typically keyed to a single target which is believed to be found on the cancer cells’ surface or in one of the cancer cells’ signaling pathways in a substantial percentage of patients with a given type of cancer. Such drugs can be of no use in patients whose cancers do not happen to express that particular target, or cease expressing that target as the disease progresses. Most cancer drugs only achieve clinical benefits in a limited percentage of the patients with the type of cancer being targeted (e.g., 25 – 30% of the patients). In contrast, DCVax has achieved clinical benefits (i.e., longer delay in disease progression and longer extension of survival than with standard of care treatment) in over 80% of the patients who have received DCVax in clinical trials to date. Since DCVax is made with biomarkers from the patient’s own tumor, it is automatically tailored to targets that are present on that patient’s cancer.

The DCVax technology is expected to be applicable to most cancers, and is embodied in several distinct product lines. One of the product lines (DCVax®-L) is designed to cover all solid tumor cancers in which the tumors can be surgically removed. Another product line (DCVax®-Direct) is designed for all solid tumor cancers which are considered inoperable and cannot be surgically removed. We believe the broad applicability of DCVax to many cancers provides multiple opportunities for commercialization and partnering.

In order to make DCVax for a patient, the patient’s immune cells are obtained through a blood draw (called a “leukapheresis” or “apheresis”). These immune cells are precursors of dendritic cells, called “monocytes.”

For DCVax-L, the monocytes are differentiated into dendritic cells, and matured, activated and loaded with biomarkers (“antigens”) from the patient’s own tumor tissue (which is collected in a simple kit at the time of surgery to remove the tumor). The loading of biomarkers into the dendritic cells “educates” them about what the immune system needs to attack. The activated, educated dendritic cells are then isolated with very high purity and comprise the DCVax-L personalized vaccine. DCVax -L is administered to the patient through a simple intra-dermal injection in the upper arm, similar to a flu shot. The dendritic cells then convey the tumor biomarker information to the rest of the immune system agents (T cells, B cells and others), as “marching orders,” and the immune system agents then fan out through the body searching for anything with these biomarkers and attacking it.

For DCVax-Direct, the monocytes are differentiated into dendritic cells and partially matured. DCVax-Direct is administered by injection directly into inoperable tumors. These injections can reach tumors located virtually anywhere in the body, with ultrasound image guidance. After injection into the tumors, the DCVax-Direct dendritic cells pick up the tumor biomarkers (“antigens”) in situ in the tumor. Then, like the DCVax-L product, the dendritic cells in the DCVax-Direct product then convey the tumor biomarker information to the rest of the immune system agents (T cells, B cells and others), who then act upon it throughout the body.

Importantly, each activated, educated dendritic cell has a large multiplier effect, mobilizing hundreds of T cells and other immune cells. As a result, small doses of such dendritic cells can mobilize large and sustained immune responses.

Also very importantly, DCVax-L is non-toxic. In clinical trials to date, stretching over a decade and including over 1,000 treatment cycles, there have been no toxicities such as chemotherapies involve – no “serious adverse events” – related to the treatment.