Fighting Cancer Using God's Design
Far too many people know the ravages of cancer. Whether through firsthand experience or caring for loved ones, most have felt the devastating impact of a disease that has invaded the narrative of nearly every family’s ongoing story. Yet, while the personal battles, triumphs, and treatment successes are well known, society at large understands little about the disease’s biological background and the strategies for treatment. As the undergraduate students in my Azusa Pacific research program discovered, different types of cancer call for different approaches. Exploring beyond the current standard of therapy, we have been working on a novel strategy for treatment—immunotherapy, a way of boosting the body’s natural defenses to fight the disease.
To understand how this works, one must first understand the basics of cancer, a disease of fast-growing cells that develops following a number of DNA mutations (normally a minimum of 4-7). These mutations typically alter genes that function to regulate cell division or repair of DNA damage. These changes enable the cell to grow without growth controls, ultimately allowing the cell to invade surrounding tissue and metastasize to distant sites. The genetic alterations that enable tumor formation vary from one cancer to the next, making each cancer type a different form of the disease. As a result, the typical standard of care includes radiation and chemotherapy, which target cells that grow rapidly. However, many noncancerous, fast-growing cell types also succumb to these treatments, making standard cancer therapy harmful to healthy tissue. This underscores the need for more specific forms of treatment to eliminate the cancer cells without damaging the normal body.
Immunotherapy aims to harness the natural power of the immune system to target and eliminate tumor cells. Although the immune system has the capability to recognize and target tumor cells to some extent, it is limited because the immune system is programmed to target foreign invaders. Cancer cells, while behaving inappropriately, are part of the normal body, something the immune system is wired to protect. One immunotherapeutic approach, adoptive immunotherapy, utilizes genetic modification to reprogram immune cells to target tumor cells specifically. In order to do so, immune cells are engineered to express a DNA sequence that will code for a protein receptor that is specific to the tumor. This protein receptor allows for the engineered cells to recognize the tumor and, upon contact, immediately initiate a killing response (Figure 1). This highly specific form of therapy utilizes engineered cells that target and kill only cancerous cells. In addition, these protein receptors can be designed for any target, giving the potential for application to all tumor types.
This immunotherapeutic approach has shown the greatest clinical success against B cell malignancies, a cancer of white blood cells. In fact, clinical trial results across multiple centers for treatment of acute lymphoblastic leukemia (one form of B cell malignancy) specifically show remission rates ranging from 67-100 percent and exhibit a high level of safety in patients. This approach is in varied stages of clinical development for several other cancers, including, but not limited to: melanoma, neuroblastoma, glioblastoma, and breast, ovarian, cervical, and prostate cancers. My APU research program has the privilege of pursuing adoptive immunotherapy in collaboration with the laboratory of Stephen Forman, MD, at City of Hope, which has designed several platforms, including one that is in clinical trial for glioblastoma, an aggressive form of brain cancer. My research team is focused on enhancing this immunotherapeutic approach by addressing the immunosuppressive nature of the tumor. In general, signals that inhibit immune function are turned on, while signals that stimulate immune function are turned off, within the tumor. The APU lab designs additional genetic engineering platforms that marry an “off” signal with an “on” signal in order to trick the tumor into stimulating the immune system. These platforms will be assessed in conjunction with the strategies developed for glioblastoma, and it is my hope that clinical efficacy will be enhanced. This project presents a unique opportunity for undergraduate students to learn a variety of cutting-edge techniques while performing translational research with direct implications for clinical treatment.
While several advances have already been made, adoptive immunotherapy is still a young field with endless potential for application to all cancer types. This approach allows for specific targeting of the cancer cells, enabling restoration from the disease while minimizing harm to the rest of the body. I anticipate that immunotherapeutic approaches will move on from clinical trial and become a new standard of care. In my opinion, there is no better way to approach cancer treatment than to harness the God-given system for protection—the immune system.
Posted: December 12, 2016