Road to a Cure - Use of Immunotherapy
This week the Road to a Cure investigators are visiting Dr. Stephanie Goff in her new office at the NIH in Bethesda, Maryland. Dr. Goff is a surgical oncologist and a senior member of a pioneering cancer research team led by Dr. Steven A. Rosenberg, Chief or Surgery at the National Caner Institute (NCI) and a man widely regarded as the father of immunotherapy. In the summer of 2015, Judy Perkins was given months to live after all treatments for her MBC had failed. She has very likely been cured by a revolutionary immunotherapy treatment, known as adoptive cell therapy, that was successfully administered by Dr. Goff and her colleagues at the National Institutes of Health.
The publication of a June 2018 issue of Nature Medicine, a respected peer-reviewed medical journal, contained an article with an incomprehensible title for a lay person - “Immune Recognition of Somatic Mutations Leading to Complete Durable Regression in Metastatic Breast Cancer.”
The beginning of the article is as follows:
“We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing, and it represents a new immunotherapy approach for the treatment of these patients.”
The “we” in the article is a team of researchers from the NCI. The new immunotherapy approach referenced in the article is generally known as cellular therapy and more specifically adoptive cell therapy, a method that essentially farms T cells, grows out the ones effective against cancer, and transfers them back to the patient.
The patient in the article was a forty-nine-year-old Florida woman with stage 4 breast cancer and large tumors throughout her body - Judy Perkins. She is alive and well today and continues to be NED or No Evidence of Disease. Our series would be incomplete without a conversation with Dr. Stephanie Goff, a senior member of Dr Rosenberg’s team and Judy’s oncologist. We are very fortunate that Judy joins us as well to speak with her doctor and recall her incredible story of being part of this ground-breaking trial.
Join us as we make over 10 stops all over the U.S. (with one stop in Europe) on this Road to a Cure - every Monday until the start of the San Antonio Breast Cancer Symposium in December!
Definitions
immunotherapy - a type of cancer treatment that boosts or changes the body’s own immune system to help it recognize, target, and destroy cancer cells more effectively
cellular therapies - any cancer treatment that uses a whole living cell as the “drug” (rather than just a folded protein or other molcule as the therapeutic agent)
adoptive cell therapy - a method that essentially farms T cells, grows out the ones effective against cancer, and transfers them back to the patient
CAR T-cell therapy (chimeric antigen receptor) - a personalized immunotherapy that genetically engineers a patient’s own immune cells (T cells) to recognize and destroy cancer cells
hot/cold tumors - classifications based on how heavily a tumor is infiltrated by immune cells, particularly T cells, which determines their response to immunotherapy
tumor micro environment - the complex ecosystem surrounding cancer cells, consisting of blood vessels, immune cells, fibroblasts, other stromal cells, and the extracellular matrix (ECM)
stroma - the supportive, structural framework of an organ, tissue, or cell, distinct from it’s functional components
Further Reading
Abbas, Abul K., Andrew H. Lichtman, and Shiv Pillai. “Cellular and Molecular Immunology” Philadelphia: Elsevier Inc., 2015.
Bibel, Debra Jan. “Milestones in Immunology: A Historical Exploration” Madison, WI: Science Tech Publishers, 1988.
Clark, William. “A War Within: The Double-Edged Sword of Immunity” New York: Oxford University Press, 1995.
Mukherjee, Siddhartha. “The Emperor of All Maladies” New York: Scribner, 2010.
Mukherjee, Siddhartha. The Gene: An Intimate History (ISBN978-1476733500), 2016
Rosenberg, Steven A., and John M. Barry. “The Transformed Cell” New York: G. P. Putnam’s Sons, 1992.
Graeber, Charles. “The Breakthrough (Immunotherapy and the Race to Cure Cancer)” Grand Central Publishing.
DeVita, Jr., Vincent T., M.D.; DeVita-Raeburn, Elizabeth. “The Death of Cancer” Farrar, Straus and Giroux.
Mentioned in this Episode
Immunotherapy
Nikolaos Zacharakis et al., “Immune Recognition of Somatic Mutations Leading to Complete Durable Regression in Metastatic Breast Cancer,” Nature Medicine, 2018, 24:724–730.
James N. Kochenderfer et al., “Eradication of B-Lineage Cells and Regression of Lymphoma in a Patient Treated with Autologous T Cells Genetically Engineered to Recognize CD19,” Blood, 2010, 116:4099–4102, doi:10.1182/blood-2010-04-281931. 21.
James N. Kochenderfer et al., “B-Cell Depletion and Remissions of Malignancy along with Cytokine-Associated Toxicity in a Clinical Trial of Anti-CD19 Chimeric-Antigen-Receptor-Transduced T cells,” Blood 119, no. 12 (2012): 2709–20.
