Immunotherapy for Cancer Named Advance of the Year by ASCO
Ashley E. Glode, PharmD BCOP
Assistant Professor, Department of Clinical Pharmacy
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
Clinical Pharmacy Specialist
University of Colorado Cancer Center
Aurora, CO
Immunotherapy has been a cancer treatment strategy since the late 19th century, though not widely implemented into practice until today. In 1891, New York surgeon William Coley injected bacteria into a patient’s tumors in an attempt to elicit an immune response targeting the infection as well as the tumor.1 Several methods to harness the immune system to attack cancer cells have been investigated over the decades, including stimulating the actions of specific components within the immune system or thwarting signals made by cancer cells to suppress the immune response.2 Unfortunately using the body’s own immune system to target cancer cells is not an easy feat to master. Cancer cells may evade the immune system by concealing themselves to make it difficult for T cells to identify them, or by expressing proteins that suppress T cells in the surrounding environment.
Numerous immunotherapy treatment methods have been researched and refined leading to U.S. Food and Drug Administration (FDA) approved treatment options. Immune checkpoint modulators are agents that modulate certain proteins to limit the strength and duration of the immune response.2 By blocking these proteins, the immune system is no longer in check and can fully attack and destroy cancer cells. Ipilimumab was the first medication approved that inhibits the checkpoint CTLA4. Nivolumab and pembrolizumab are the most recently approved agents that act on a different checkpoint, PD-1.
Adoptive cell transfer (ACT) is another exciting area of immunotherapy research. One form of this treatment collects tumor-infiltrating lymphocytes (TIL) from a patient’s tumor, manipulates and grows them in the lab with cytokines, and infuses them back into the patient.2 The theory behind this approach is that the TILs have the ability to target the tumor cell, but may not be enough to kill the tumor or overcome the immune system inhibiting their activity. Administering a large amount of these cells can overcome obstacles to shrink or kill the cancer. Another approach utilizing ACT is chimeric antigen receptor (CAR)T cell therapy, which takes a patient’s own T cells and modifies them in a lab to express a protein, or CAR. These altered T cells are multiplied and then infused into the patient to attach to proteins on the surface of the cancer cell. Once the cells are bound together, the engineered T cell is activated and kills the cancer cell.
Several therapeutic antibodies have been in practice for decades, but modifications have recently been introduced. Antibodies are designed to attack specific antigens found on cancer cells and other noncancer cells and proteins in order to kill cancer cells.3 Naked monoclonal antibodies (mAb) are most commonly used and work on their own. They induce apoptosis, antibody-dependent cell-mediated cytotoxicity, and complement-dependent cytotoxicity.2 Conjugated monoclonal antibodies are mAbs that are joined to a chemotherapy agent or radioactive particle to deliver the toxic substance directly to the cancer cell.3 The newest kind of mAb is the bispecific monoclonal antibody, which combines two different mAbs allowing the drug to bind to two different proteins at the same time. Blinatumomab is an approved agent that binds to both CD19 and CD3.
Therapeutic cancer vaccines also have been an area of research for decades. The first ap- proved therapeutic vaccine was sipuleucel-T.3 To engineer this vaccine, cells are taken from the patient and treated prior to being reinfused and helping the immune system attack the cancer. Many different types of cancer vaccines (tumor cell vaccines, antigen vaccines, dendritic cell vaccines, vector-based vaccines) are currently being investigated in a variety of malignancies including brain, breast, and lung cancer. It is an exciting area of development.
The American Society of Clinical Oncology (ASCO) has named cancer immunotherapy the advance of the year due to the number of improvements made to the immunomodulary process and the clinical implementation of immunotherapy strategies into multiple disease states.3 Research is expanding the number of patients who may benefit from these strategies and developing ways to minimize adverse effects to improve tolerability.
References
1. Ledford H. The killer within. Nature. 2014. 508:24-26.
2. National Cancer Institute. Immunotherapy: using the immune system to treat cancer.
Updated: Sept 14, 2015.
3. American Cancer Society. Cancer Immunotherapy. 2015. Last revised: Nov 5, 2015.
4. ASCO Clinical Cancer Advances 2016. ASCO’s 11th Annual Report on Progress against
Cancer. Published in the J Clin Oncol online ahead of print Feb 4, 2016.