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ASH-EHA: An Intercontinental Voyage Into Cancer Immunity

December 12, 2021
Tania Jain, MBBS

Dr. Tania Jain (@TaniaJain11) is an assistant professor and director of the Adult CAR T Program at Johns Hopkins University. Her academic interest is in cellular therapy, bone marrow transplantation, and myeloproliferative neoplasms including overlap with myelodysplastic syndromes. She is a graduate of Government Medical College, Patiala (Punjab), India, where she received her medical degree, before going on to a residency at Wayne State University/ Detroit Medical Center, and fellowships at Mayo Clinic in Arizona and at Memorial Sloan Kettering Cancer Center for bone marrow transplantation. 

Dr. Jain grew up in Chandigarh, India, and has since been, in her words, “nomadic … our current residence in Baltimore is what we call home now.” She is a longtime enthusiastic attendee of the ASH annual meeting since second year of fellowship (no breaks) as well as speaker at Highlights of ASH® in North America in 2020. Prior to travel restrictions, Dr. Jain enjoys chipping away at some very specific and ambitious travel goals with her husband. “Our travel adventures of late revolved around visiting the four (north, south, east, and west) extreme points of the United States. We have thus far been to Point Barrow in Alaska (northernmost), Point Buoy in Key West, Florida (southernmost for the continental United States), and almost to (less than 10 miles away from) Ka Lae (South Cape) in Hawaii, which is southernmost for the US overall,” she explained. “This got interrupted with COVID, but we are excited to get back to our travel adventures.” Fingers crossed, and happy trails, Dr. Jain! 

Harnessing the immune system is thought to be the newer and “sexier” way to treat cancer. In reality, this recognition dates back to antiquity. Allow me to indulge you in some of the past and present of immunotherapy. Dr. William Bradley Coley, who is now known as the father of cancer immunotherapy, first attempted to treat cancer using the immune system in 1981 by injecting Streptococcus and inducing erysipelas. This “Coley’s toxin” dissolved a malignant tonsillar mass in a patient and subsequently in 10 additional patients. Back in the day, however, this was met with the familiar and abundant skepticism, followed by a label of “alleged remedy.” But fate has a twisted sense of humor, and this was destined to be recognized as one of the most promising cancer therapies in the years to come. Half a century later, the role of T cells in immunity was published as a pivotal study in Nature (Dr. Jacques Miller, 1967), succeeded by the discovery of dendritic cells (Dr. Ralph Steinman, 1973), and a description of natural killer (NK) cells (Dr. Eva Klein, 1975). Concomitantly, early trials of bone marrow transplantation to treat hematologic malignancies were emerging. Together, they resuscitated immunotherapy and set in motion the wheels of cancer immunotherapy as we now know it. This culminated in Drs. James P. Allison and Tasuku Honjo receiving the Nobel Prize in Physiology or Medicine in 2018 for their discovery of cancer treatment by inhibition of negative immune regulation. Recently, we have continued to witness the evolving carnage of cancer by genetically engineered T cells (first reported by Drs. Gilean Gross and Zelig Eshhar in 1989), popularly known as chimeric antigen receptor T cells, or “CAR T cells.” This is truly one of those things that reminds you of Churchill’s very apt quote, “This is not the end; this is not even the beginning of the end…” 

The 2021 joint symposium of ASH and the European Hematology Association (EHA) “Targeting Macrophages and the Innate Immune System to Treat Hematologic Malignancies,” taking place virtually and in-person Sunday at 12:30 p.m. Eastern time, in Hall C2-C3 of the Georgia World Congress Center, showcases the broader scope of immunotherapy, from the fashionable adaptive immune system to the less-famous but gaining exponential popularity, innate immune system. This session, chaired by Dr. Elizabeth A. Macintyre and ASH President Dr. Martin Tallman, will showcase two talks — one on CD47 signaling in acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL), and the other on NK cells in AML. 

CD47CD47 in cancer cells delivers a formidable “don’t eat me” signal to the immune system by binding to the signal-regulatory protein a (SIRPa), crippling the macrophage-mediated phagocytosis. Mathematical magic has taught us that multiplying two negatives makes a positive. Similarly, blocking this inhibitory signal can open up opportunities to target cancer cells. Fortunately, this is not fiction any longer, and a humanized anti-CD47 antibody is now in the developmental pipeline. In the ASH-EHA session, Dr. Ravi Majeti will highlight the whole nine yards of bench-to-bedside for CD47 in AML and NHL. 

NK cells are another indispensable component of the innate immune system. AML stem cells are smart enough to lower their expression of NKG2D ligand to stun NK cells. Dr. Claudia Lengerke, and her team have, however, hammered away at the mechanism of how the cancer cells manage to do so via enhanced PARP1 expression in leukemia stem cells and how we can overcome this to facilitate AML cell killing via the forgotten hero, NK cells. These will include combined approaches such as PARP1 inhibitors and CAR-NK cells, which Dr Lengerke will discuss during this talk. This will be the second talk of this session enlightening us on yet another positive result from a “double negative” mechanism to promote cancer cell death.  

When ASH and EHA get together, I anticipate fireworks! And fireworks are what this session will offer. 

Dr. Jain indicated no relevant conflicts of interest. 

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